Lost in translation: when the endocrine and central nervous systems fail to communicate

Two major coordinators orchestrate communication within our bodies: the nervous system and the endocrine system. The nervous system allows signals to move rapidly from the brain and spinal cord all the way to the different parts of the body via neurons. It coordinates both voluntary and involuntary movements that ensure the basic functioning of the body. The endocrine system, in turn, uses hormones to communicate longer-term messages that fine-tune a number of functions, including digestion, blood pressure, growth, reproduction and lactation. These two communication systems are intertwined at the hypothalamus, a structure located at the base of the forebrain. The hypothalamus integrates upstream messages received from the nervous system and controls the pituitary gland, the master player of the endocrine system. A number of rare genetic disorders can affect the nervous and endocrine systems. They cause respectively intellectual deficiencies (including Rett syndrome and a number of Early Onset Epileptic Encephalopathies) or imbalances in hormone secretion, which impact on a myriad of bodily functions.

Scientists and clinicians at the CNS/NET department have been major players in identifying and diagnosing rare disorders affecting the nervous and neuroendocrine systems, deciphering their genetic causes, understanding the mechanisms leading to disease and ultimately, developing therapies to treat patients.

The CNS/NET department unites a unique set of skills, including clinical expertise at the bedside, molecular genetics, neurophysiology, neuroendocrinology and preclinical research that has been crucial to promote important research breakthroughs and fast-track them into clinical development to treat diseases affecting the central nervous system and/or the neuroendocrine system.



Improving the knowledge of neurodevelopmental diseases

Intellectual deficiency (ID) is defined as a disability characterized by significant limitations both in intellectual functioning and in adaptive behaviour, i.e. a person's social responsibility and independent performance of daily activities. ID touches as much as 3% of the population and represents a major public health problem in all countries. Considerable progress has been made over the past twenty years in the field of early diagnosis, but 50% of ID patients still remain undiagnosed. To improve this situation, the team of Laurent Villard, among others, studies the genetic causes of ID. They have identified several genes responsible for various form of neurodevelopmental disorders, and have made significant contributions in the understanding of the mechanisms that are defective when these genes are mutated.

A unique cohort of 1300 affected patients

In their efforts to improve diagnosis of a group of rare epilepsies associated with severe ID, Developmental and Epileptic Encephalopathies (DEE), the group manages a large cohort of 1300 affected patients. This invaluable resource has already proven instrumental in identifying several new genes associated with DEE. Among them was the unexpected identification of KCNQ2 as the most frequently mutated gene.

“KCNQ2 was traditionally found in patients with benign familial neonatal convulsions (BFNC), a condition for which the neurological prognosis is generally good and development is normal.” explains Mathieu Milh, the neurologist heading the clinical aspects of this research in Laurent Villard’s laboratory. “It was a real surprise to find that KCNQ2 is actually a major EOEE gene, since we identified 68 mutations in the patients in our cohort”.

KCNQ2 encodes a protein that makes potassium channels in neurons and is crucial for proper communication within the brain. In collaboration with INMED (Inserm U1249) and La Timone Neurosciences Institute INT (CNRS), the scientists are currently investigating what might be different at the cellular level in the two populations of patients that are affected by either BFNC or the much more severe condition EOEE. The ultimate goal of this program is to offer EOEE patients new pharmacological therapies to overcome the current lack of effective treatments. These projects were previsouly supported by ANR grants, and are funded again within the 2019 ANR call, for a project called IMprove (2019-2022).

The enterprise is much further along in the field of Rett Syndrome, another intellectual deficiency that has occupied researchers in Laurent Villard’s laboratory for many years.

Rett Syndrome: a rare neurological disorder

Rett Syndrome (RTT) was first described in 1966 by the Austrian paediatrician Andreas Rett. It affects mostly girls and is characterized by a normal development up until the age of 6 to 18 months. Brain development then slows down until it eventually stops. As a severe intellectual deficiency settles, head growth stagnates leading to an acquired microcephaly, and previously learned skills such as speech or walk can be lost. Many patients face additional complications including motor defects, epilepsies, seizures and abnormal breathing patterns often leading to hyperventilation or apnoeas.

In 1999, the laboratory of Huda Zoghbi (Houston, Texas, USA) discovered that mutations in a gene called MECP2 are responsible for most cases of RTT.  MECP2 is located on the X chromosome, at position Xq28. Importantly, an exhaustive search for mutations in MECP2 among French patients and their families was carried out in the laboratory of Laurent Villard, and revealed that defects in this gene can also causes other types of intellectual disabilities, including severe cases of encephalopathies in boys.

From the molecular mechanisms behind RTT to the development of treatments

To better understand the mechanisms at work during RTT, Laurent Villard and his colleagues have carried a long-lasting characterisation of a mouse model of Rett Syndrome from Adrian Bird’s laboratory (Edinburgh, UK). Their work has lead to major contributions in the field, opening important avenues for treatment of Rett Syndrome patients.

The group has found that Mecp2-deficient mice display an altered breathing pattern, similar to RTT patients.  These mice also present low levels of a chemical messenger, norepinephrine (NE), in the area of the brain where the respiratory centres are located: the medulla. At the time, this finding was the first demonstration of a cellular defect caused by the absence of Mecp2 in vivo. Importantly, the experiments carried out by the team suggested that the breathing defects could be corrected with exogenous NE. The team therefore decided to develop a means to artificially increase the levels of NE in the animals by using a chemical compound called desipramine.

“ We administered a daily dose of desipramine to Rett syndrome mice, and noted a remarkable improvement of breathing but also of survival in these mice” indicates Jean-Christophe Roux in charge of the Rett syndrome projects in the Villard lab. “With these promising results, we decided to initiate a clinical trial in collaboration with Prof. Josette Mancini at La Timone Hospital, to study the effects of desipramine on children with Rett Syndrome”. The results of this phase II trial are now published.

More recently, the group also discovered a defect in transport of BDNF along neurons in RTT mice. BDNF is a crucial factor that supports survival and growth of neurons, as well as the establishment of connections between them. Importantly, artificially increasing BDNF secretion using a compound called cysteamine significantly alleviates motor defects of Rett syndrome mice and improves their lifespan. This finding has now been taken to the clinic, where another phase II clinical trial is being initiated to determine the efficacy of a cysteamine treatment in RTT patients.

Efforts to understand the molecular dysfunctions in RTT have proven fruitful. The team is currently exploring new horizons that already appear promising in this same direction, offering new translational perspectives for this disorder.

 

Neuroendocrine disorders result from a gland secreting either too much or too little of an endocrine hormone. While the vast majority of oversecreting diseases is caused by benign, non-cancerous tumours, called neuroendocrine tumours, undersecreting disorders, or hormone deficiencies, can have a variety of origins. They may affect any gland in the endocrine system, but those that affect the pituitary gland, the master of this system, will have a broader spectrum of consequences on different biological functions. To identify new therapeutic strategies, the laboratory of Thierry Brue has been interested over the past decades in understanding the genetic causes and the molecular mechanisms responsible for these disorders. The scientists have focused on combined pituitary hormone deficiency (CPHD), for which they have identified a number of responsible genes and mutations, partly through the creation of an international collection of DNA samples from over 1200 patients (GENHYPOPIT).

Neuroendocrine disorders: keeping the right balance

“Through a detailed analysis of the DNA samples from the GENHYPOPIT network, we were able to uncover a new syndrome that combines hormone deficiency with a variable immune deficiency, characterized by defective antibody production” declares Thierry Brue. “We have named it DAVID, for Deficit in Anterior pituitary function and Variable Immune Deficiency”. The gene responsible for DAVID syndrome is called NFKB2 and encodes a subunit of the NFB complex, a central activator of genes involved in inflammation and the immune response.

The lab has also widely studied neuroendocrine tumours (NET) to uncover the signals that are responsible for the increase in hormone secretion.  Interestingly, the team has identified several factors involved in and with opposite effects on CPHD and NET. Such is the case for the Growth Hormone Receptor (GHR) and for the Ghrelin receptor (GHS-R), as well as for Pit-1, a transcription factor important for pituitary development and hormone expression.

The dual role of Pit-1

Alterations of the PIT-1 gene sequence or expression level have been linked to cases of both dwarfism and gigantism. It encodes a transcription factor that is important for the differentiation of endocrine cells, as well as for regulating the expression of hormones such as Growth Hormone or Prolactin (involved in growth and lactation, respectively). Mutations in the PIT-1 gene had been previously associated with cases of CPHD when, in 2006, Thierry Brue, Anne Barlier and their colleagues demonstrated its importance in NET, where it acts as a growth promoter. Because of the dual role that Pit-1 appeared to have in hormone deficiencies and oversecreting disorders, the team attempted a gene therapy approach where a mutant version of Pit-1 found in CPHD patients, Pit-1-R271W, was used to treat oversecretion and tumoral growth of the opposite disease, pituitary tumours.

“We demonstrated that the Pit1-R271W mutant is able to block hormonal oversecretion of NET cells and to induce cell death both in vitro and in vivo in mice” explains Anne Barlier, who has led this research in Thierry Brue’s laboratory. “This strategy could turn promising for the gene therapy of human pituitary tumours”.

In addition to pursuing the hunt for genetic abnormalities linked to neuroendocrine diseases, the scientists are now investing major efforts in establishing new cellular models to study hormone deficiencies and neuroendocrine tumours, and developing new therapies to treat both of these affections.

 

Milh, M.  et al. 2020

A knock-in mouse model for KCNQ2-related epileptic encephalopathy displays spontaneous generalized seizures and cognitive impairment

OBJECTIVE: Early onset epileptic encephalopathy with suppression-burst is one of the most severe epilepsy phenotypes in human patients. A significant proportion of cases have a genetic origin, and the...
Epilepsia - issue: 5 - volume: 61 - pages: 868-878.

Ehinger, Y.  et al. 2020

Huntingtin phosphorylation governs BDNF homeostasis and improves the phenotype of Mecp2 knockout mice

Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder for which there is no treatment. Several studies have linked the loss of MeCP2 function to...
EMBO Mol Med - issue: 2 - volume: 12 - pages: e10889.

Mignot, C.  et al. 2019

IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

PURPOSE: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences. METHODS: We...
Genet. Med. - issue: 4 - volume: 21 - pages: 837-849.

Valence, S.  et al. 2019

Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies

PURPOSE: To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify...
Genet. Med. - issue: 3 - volume: 21 - pages: 553-563.

O'Donnell-Luria, AH.  et al. 2019

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker...
Am. J. Hum. Genet. - issue: 6 - volume: 104 - pages: 1210-1222.

Piard, J.  et al. 2019

The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature

PURPOSE: Germline WWOX pathogenic variants have been associated with disorder of sex differentiation (DSD), spinocerebellar ataxia (SCA), and WWOX-related epileptic encephalopathy (WOREE syndrome). We...
Genet. Med. - issue: 6 - volume: 21 - pages: 1308-1318.

Mignot, C.  et al. 2019

IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

PURPOSE: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences. METHODS: We...
Genet. Med. - issue: 4 - volume: 21 - pages: 837-849.

Denis, J.  et al. 2019

Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures

OBJECTIVE: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. METHODS: We reviewed...
Epilepsia - issue: 5 - volume: 60 - pages: 845-856.

Frullanti, E.  et al. 2019

Analysis of the Phenotypes in the Rett Networked Database

Rett spectrum disorder is a progressive neurological disease and the most common genetic cause of intellectual disability in females. MECP2 is the major causative gene. In addition, CDKL5 and FOXG1...
Int J Genomics - issue: - volume: 2019 - pages: 6956934.

Valence, S.  et al. 2019

Exome sequencing in congenital ataxia identifies two new candidate genes and highlights a pathophysiological link between some congenital ataxias and early infantile epileptic encephalopathies

PURPOSE: To investigate the genetic basis of congenital ataxias (CAs), a unique group of cerebellar ataxias with a nonprogressive course, in 20 patients from consanguineous families, and to identify...
Genet. Med. - issue: 3 - volume: 21 - pages: 553-563.

O'Donnell-Luria, AH.  et al. 2019

Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker...
Am. J. Hum. Genet. - issue: 6 - volume: 104 - pages: 1210-1222.

Piard, J.  et al. 2019

The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature

PURPOSE: Germline WWOX pathogenic variants have been associated with disorder of sex differentiation (DSD), spinocerebellar ataxia (SCA), and WWOX-related epileptic encephalopathy (WOREE syndrome). We...
Genet. Med. - issue: 6 - volume: 21 - pages: 1308-1318.

Denis, J.  et al. 2019

Clinical study of 19 patients with SCN8A-related epilepsy: Two modes of onset regarding EEG and seizures

OBJECTIVE: To describe the mode of onset of SCN8A-related severe epilepsy in order to facilitate early recognition, and eventually early treatment with sodium channel blockers. METHODS: We reviewed...
Epilepsia - issue: 5 - volume: 60 - pages: 845-856.

Mignon-Ravix, C.  et al. 2018

Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst

Early myoclonic epilepsy (EME) or Aicardi syndrome is one of the most severe epileptic syndromes affecting neonates. We performed whole exome sequencing in a sporadic case affected by EME and his...
Hum. Mutat. - issue: 7 - volume: 39 - pages: 934-938.

Ehinger, Y.  et al. 2018

Rett syndrome from bench to bedside: recent advances

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role in chromatin organization and...
F1000Res - issue: - volume: 7 - pages: 398.

Mancini, J.  et al. 2018

Effect of desipramine on patients with breathing disorders in RETT syndrome

Objective: Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced...
Ann Clin Transl Neurol - issue: 2 - volume: 5 - pages: 118-127.

Mortreux, J.  et al. 2018

The role of CNVs in the etiology of rare autosomal recessive disorders: the example of TRAPPC9-associated intellectual disability

INTRODUCTION: A large number of genes involved in autosomal recessive forms of intellectual disability (ID) were identified over the past few years through whole-exome sequencing (WES) or whole-genome...
Eur. J. Hum. Genet. - issue: 1 - volume: 26 - pages: 143-148.

Mignon-Ravix, C.  et al. 2018

Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst

Early myoclonic epilepsy (EME) or Aicardi syndrome is one of the most severe epileptic syndromes affecting neonates. We performed whole exome sequencing in a sporadic case affected by EME and his...
Hum. Mutat. - issue: 7 - volume: 39 - pages: 934-938.

Mortreux, J.  et al. 2018

The role of CNVs in the etiology of rare autosomal recessive disorders: the example of TRAPPC9-associated intellectual disability

INTRODUCTION: A large number of genes involved in autosomal recessive forms of intellectual disability (ID) were identified over the past few years through whole-exome sequencing (WES) or whole-genome...
Eur. J. Hum. Genet. - issue: 1 - volume: 26 - pages: 143-148.

Ehinger, Y.  et al. 2018

Rett syndrome from bench to bedside: recent advances

Rett Syndrome is a severe neurological disorder mainly due to de novo mutations in the methyl-CpG-binding protein 2 gene ( MECP2). Mecp2 is known to play a role in chromatin organization and...
F1000Res - issue: - volume: 7 - pages: 398.

Mancini, J.  et al. 2018

Effect of desipramine on patients with breathing disorders in RETT syndrome

Objective: Rett Syndrome (RTT) is a severe neurodevelopmental condition with breathing disorders, affecting around one in 10,000 female births. Desipramine, a noradrenaline reuptake inhibitor, reduced...
Ann Clin Transl Neurol - issue: 2 - volume: 5 - pages: 118-127.

Marzin, P.  et al. 2018

Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations

OBJECTIVE: Heterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset...
Brain Dev. - issue: 9 - volume: 40 - pages: 768-774.

Marzin, P.  et al. 2018

Early-onset encephalopathy with paroxysmal movement disorders and epileptic seizures without hemiplegic attacks: About three children with novel ATP1A3 mutations

OBJECTIVE: Heterozygous mutations in the ATP1A3 gene are responsible for various neurological disorders, ranging from early-onset alternating hemiplegia of childhood to adult-onset...
Brain Dev. - issue: 9 - volume: 40 - pages: 768-774.

Bramswig, NC.  et al. 2018

Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies)

NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the...
Hum. Genet. - issue: 9 - volume: 137 - pages: 753-768.

Bramswig, NC.  et al. 2018

Genetic variants in components of the NALCN-UNC80-UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies)

NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the...
Hum. Genet. - issue: 9 - volume: 137 - pages: 753-768.

Sauvestre, F.  et al. 2017

In utero seizures revealing dentato-olivary dysplasia caused by SCN2A mutation


Neuropathol. Appl. Neurobiol. - issue: 7 - volume: 43 - pages: 631-635.

Petrossians, P.  et al. 2017

Acromegaly at diagnosis in 3173 patients from the Liège Acromegaly Survey (LAS) Database

Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly...
Endocr. Relat. Cancer - issue: 10 - volume: 24 - pages: 505-518.

Villeneuve, N.  et al. 2017

Heterogeneity of FHF1 related phenotype: Novel case with early onset severe attacks of apnea, partial mitochondrial respiratory chain complex II deficiency, neonatal onset seizures without neurodegeneration

INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in our institution for a severe, neonatal onset epilepsy presenting with severe attacks of apnea that were not initially...
Eur. J. Paediatr. Neurol. - issue: 5 - volume: 21 - pages: 783-786.

Villeneuve, N.  et al. 2017

Heterogeneity of FHF1 related phenotype: Novel case with early onset severe attacks of apnea, partial mitochondrial respiratory chain complex II deficiency, neonatal onset seizures without neurodegeneration

INTRODUCTION/OBJECTIVES: We report the case of a child prospectively followed in our institution for a severe, neonatal onset epilepsy presenting with severe attacks of apnea that were not initially...
Eur. J. Paediatr. Neurol. - issue: 5 - volume: 21 - pages: 783-786.

Mohamed, A.  et al. 2017

Anti-proliferative and anti-secretory effects of everolimus on human pancreatic neuroendocrine tumors primary cultures: is there any benefit from combination with somatostatin analogs?

Therapeutic management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is challenging. The mammalian target of rapamycin (mTOR) inhibitor everolimus recently obtained approval from the Food...
Oncotarget - issue: 25 - volume: 8 - pages: 41044-41063.

Castinetti, F.  et al. 2017

Gamma Knife radiosurgery for hypothalamic hamartoma preserves endocrine functions

Gamma Knife radiosurgery (GK) is an effective treatment for hypothalamic hamartoma. No precise data are available on the risk of endocrine side effects of this treatment. In this study, 34 patients...
Epilepsia - issue: - volume: 58 Suppl 2 - pages: 72-76.

Brue, T.  et al. 2017

Lessons from monogenic causes of growth hormone deficiency

Through the multicentric international GENHYPOPIT network, 10 transcription factor genes involved in pituitary development have been screened in more than 1200 patients with constitutional...
Ann. Endocrinol. (Paris) - issue: 2 - volume: 78 - pages: 77-79.

Maione, L.  et al. 2017

Changes in the management and comorbidities of acromegaly over three decades: the French Acromegaly Registry

CONTEXT: Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. DESIGN: The French Registry contains data on...
Eur. J. Endocrinol. - issue: 5 - volume: 176 - pages: 645-655.

Wolff, M.  et al. 2017

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71...
Brain - issue: 5 - volume: 140 - pages: 1316-1336.

Wolff, M.  et al. 2017

Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders

Mutations in SCN2A, a gene encoding the voltage-gated sodium channel Nav1.2, have been associated with a spectrum of epilepsies and neurodevelopmental disorders. Here, we report the phenotypes of 71...
Brain - issue: 5 - volume: 140 - pages: 1316-1336.

Franck, SE.  et al. 2017

A multivariable prediction model for pegvisomant dosing: monotherapy and in combination with long-acting somatostatin analogues

BACKGROUND: Effective treatment of acromegaly with pegvisomant (PEGV), a growth hormone receptor antagonist, requires an appropriate dose titration. PEGV doses vary widely among individual patients,...
Eur. J. Endocrinol. - issue: 4 - volume: 176 - pages: 421-430.

Eroukhmanoff, J.  et al. 2017

MRI follow-up is unnecessary in patients with macroprolactinomas and long-term normal prolactin levels on dopamine agonist treatment

OBJECTIVE: Both antitumor and antisecretory efficacies of dopamine agonists (DA) make them the first-line treatment of macroprolactinomas. However, there is no guideline for MRI follow-up once...
Eur. J. Endocrinol. - issue: 3 - volume: 176 - pages: 323-328.

Matagne, V.  et al. 2017

A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of...
Neurobiol. Dis. - issue: - volume: 99 - pages: 1-11.

Matagne, V.  et al. 2017

A codon-optimized Mecp2 transgene corrects breathing deficits and improves survival in a mouse model of Rett syndrome

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder that is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). RTT is the second most prevalent cause of...
Neurobiol. Dis. - issue: - volume: 99 - pages: 1-11.

Graillon, T.  et al. 2017

Transcranial approach in giant pituitary adenomas: results and outcome in a modern series

BACKGROUND: Today, transcranial (TC) approach indications are particularly rare in pituitary adenomas (PA), representing 1.1% of all PA surgeries in our experience. In these rare and selected cases,...
J Neurosurg Sci - issue: - volume: - pages: .

Goldenberg, A.  et al. 2016

Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39...
Am. J. Med. Genet. A - issue: 11 - volume: 170 - pages: 2847-2859.

Devaux, J.  et al. 2016

A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity

Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been shown to induce a loss of function or...
Epilepsia - issue: 5 - volume: 57 - pages: e87-93.

Goldenberg, A.  et al. 2016

Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11

KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39...
Am. J. Med. Genet. A - issue: 11 - volume: 170 - pages: 2847-2859.

Devaux, J.  et al. 2016

A Kv7.2 mutation associated with early onset epileptic encephalopathy with suppression-burst enhances Kv7/M channel activity

Mutations in the KCNQ2 gene encoding the voltage-gated potassium channel subunit Kv7.2 cause early onset epileptic encephalopathy (EOEE). Most mutations have been shown to induce a loss of function or...
Epilepsia - issue: 5 - volume: 57 - pages: e87-93.

Képénékian, L.  et al. 2016

Long-term outcome of macroprolactinomas

OBJECTIVE: Management of macroprolactinomas has dramatically changed in recent decades, from surgical to medical treatment as first-line therapy, with the development of dopamine agonists (DA). But...
Ann. Endocrinol. (Paris) - issue: 6 - volume: 77 - pages: 641-648.

Potorac, I.  et al. 2016

T2-weighted MRI signal predicts hormone and tumor responses to somatostatin analogs in acromegaly

GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to...
Endocr. Relat. Cancer - issue: 11 - volume: 23 - pages: 871-881.

Albarel, F.  et al. 2016

Successful IVF pregnancy despite inadequate ovarian steroidogenesis due to congenital lipoid adrenal hyperplasia (CLAH): a case report

Steroidogenic acute regulatory protein (StAR) mutations are the most frequent aetiologies of congenital lipoid adrenal hyperplasia (CLAH). Phenotypes may vary, and puberty may be absent in affected...
Hum. Reprod. - issue: 11 - volume: 31 - pages: 2609-2612.

Brue, T.  et al. 2016

The risks of overlooking the diagnosis of secreting pituitary adenomas

Secreting pituitary adenomas that cause acromegaly and Cushing's disease, as well as prolactinomas and thyrotroph adenomas, are uncommon, usually benign, slow-growing tumours. The rarity of these...
Orphanet J Rare Dis - issue: 1 - volume: 11 - pages: 135.

Cuny, T.  et al. 2016

In vitro impact of pegvisomant on growth hormone-secreting pituitary adenoma cells

Pegvisomant (PEG), an antagonist of growth hormone (GH)-receptor (GHR), normalizes insulin-like growth factor 1 (IGF1) oversecretion in most acromegalic patients unresponsive to somatostatin analogs...
Endocr. Relat. Cancer - issue: 7 - volume: 23 - pages: 509-519.

Lemke, JR.  et al. 2016

Delineating the GRIN1 phenotypic spectrum: A distinct genetic NMDA receptor encephalopathy

Objective:To determine the phenotypic spectrum caused by mutations in GRIN1 encoding the NMDA receptor subunit GluN1 and to investigate their underlying functional pathophysiology.Methods:We collected...
Neurology - issue: 23 - volume: 86 - pages: 2171-2178.

Francou, B.  et al. 2016

Prevalence of KISS1 Receptor mutations in a series of 603 patients with normosmic congenital hypogonadotrophic hypogonadism and characterization of novel mutations: a single-centre study

STUDY QUESTION: What is the exact prevalence of Kisspeptin Receptor (KISS1R) mutations in the population of patients with normosmic congenital hypogonadotrophic hypogonadism (nCHH) by comparison with...
Hum. Reprod. - issue: 6 - volume: 31 - pages: 1363-1374.

Castinetti, F.  et al. 2016

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily...
Eur. J. Endocrinol. - issue: 6 - volume: 174 - pages: R239-247.

Castinetti, F.  et al. 2016

GPR101 Mutations are not a Frequent Cause of Congenital Isolated Growth Hormone Deficiency

Patients with Xq26.3 microduplication present with X-linked acrogigantism (X-LAG) syndrome, an early-childhood form of gigantism due to marked growth hormone (GH) hypersecretion from mixed GH-PRL...
Horm. Metab. Res. - issue: 6 - volume: 48 - pages: 389-393.

Lefebvre, M.  et al. 2016

Genetic counselling difficulties and ethical implications of incidental findings from array-CGH: a 7-year national survey

Microarray-based comparative genomic hybridization (aCGH) is commonly used in diagnosing patients with intellectual disability (ID) with or without congenital malformation. Because aCGH interrogates...
Clin. Genet. - issue: 5 - volume: 89 - pages: 630-635.

Zillhardt, JL.  et al. 2016

Mosaic parental germline mutations causing recurrent forms of malformations of cortical development

To unravel missing genetic causes underlying monogenic disorders with recurrence in sibling, we explored the hypothesis of parental germline mosaic mutations in familial forms of malformation of...
Eur. J. Hum. Genet. - issue: 4 - volume: 24 - pages: 611-614.

Abidi, A.  et al. 2016

Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient

Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically...
Eur. J. Hum. Genet. - issue: 4 - volume: 24 - pages: 615-618.

Caron, PJ.  et al. 2016

Effects of lanreotide Autogel primary therapy on symptoms and quality-of-life in acromegaly: data from the PRIMARYS study

PURPOSE: To evaluate the effects of lanreotide Autogel on patient-reported outcomes and association with biochemical control, using PRIMARYS data. METHODS: PRIMARYS was a 1-year, open-label study of...
Pituitary - issue: 2 - volume: 19 - pages: 149-157.

Bernard, V.  et al. 2016

Spontaneous fertility and pregnancy outcomes amongst 480 women with Turner syndrome

STUDY QUESTION: What are the prevalence and the outcomes of spontaneous pregnancies (SP) in a large cohort of French women with Turner syndrome (TS)? SUMMARY ANSWER: Amongst 480 women with TS, 27...
Hum. Reprod. - issue: 4 - volume: 31 - pages: 782-788.

Abidi, A.  et al. 2016

Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient

Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically...
Eur. J. Hum. Genet. - issue: 4 - volume: 24 - pages: 615-618.

Fiot, E.  et al. 2016

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome

OBJECTIVE: Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to...
Eur. J. Endocrinol. - issue: 3 - volume: 174 - pages: 281-288.

Milh, M.  et al. 2016

Severe neonatal seizures: From molecular diagnosis to precision therapy?

Early onset epileptic encephalopathies (EOEE) are heterogeneous group of severe epilepsies that still need to be better defined and characterized. On a genetic point of view, several dozen of genes...
Rev. Neurol. (Paris) - issue: 3 - volume: 172 - pages: 171-173.

Lacoste, C.  et al. 2016

Coverage Analysis of Lists of Genes involved in Heterogeneous Genetic Diseases following Benchtop Exome Sequencing using the Ion Proton


J. Genet. - issue: 1 - volume: 95 - pages: 203-208.

Lacoste, C.  et al. 2016

Coverage Analysis of Lists of Genes involved in Heterogeneous Genetic Diseases following Benchtop Exome Sequencing using the Ion Proton


J. Genet. - issue: 1 - volume: 95 - pages: 203-208.

Guerin, C.  et al. 2016

Bilateral adrenalectomy in the 21st century: when to use it for hypercortisolism?

Therapeutic options available for the treatment of Cushing's syndrome (CS) have expanded over the last 5 years. For instance, the efficient management of severe hypercortisolism using a combination of...
Endocr. Relat. Cancer - issue: 2 - volume: 23 - pages: R131-142.

Castinetti, F.  et al. 2016

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers...
Eur. J. Endocrinol. - issue: 1 - volume: 174 - pages: R9-18.

Philippon, M.  et al. 2015

Successful pregnancies and healthy live births using frozen-thawed sperm retrieved by a new modified Hotchkiss procedure in males with retrograde ejaculation: first case series

BACKGROUND: In couples presenting with retrograde ejaculation refractory to medical treatment, the first choice of fertility treatment should be Assisted Reproductive Techniques using rapidly purified...
Basic Clin Androl - issue: - volume: 25 - pages: 5.

Jullien, N.  et al. 2015

Dose-dependent dual role of PIT-1 (POU1F1) in somatolactotroph cell proliferation and apoptosis

To test the role of wtPIT-1 (PITWT) or PIT-1 (R271W) (PIT271) in somatolactotroph cells, we established, using inducible lentiviral vectors, sublines of GH4C1 somatotroph cells that allow the blockade...
PLoS ONE - issue: 3 - volume: 10 - pages: e0120010.

Choucair, N.  et al. 2015

Evidence that homozygous PTPRD gene microdeletion causes trigonocephaly, hearing loss, and intellectual disability

BACKGROUND: The premature fusion of metopic sutures results in the clinical phenotype of trigonocephaly. An association of this characteristic with the monosomy 9p syndrome is well established and the...
Mol Cytogenet - issue: - volume: 8 - pages: 39.

Choucair, N.  et al. 2015

Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients

BACKGROUND: Chromosomal microarray analysis (CMA) is currently the most widely adopted clinical test for patients with unexplained intellectual disability (ID), developmental delay (DD), and...
Mol Cytogenet - issue: - volume: 8 - pages: 26.

Di Meglio, C.  et al. 2015

Epileptic patients with de novo STXBP1 mutations: Key clinical features based on 24 cases

OBJECTIVE: Mutations in the syntaxin binding protein 1 gene (STXBP1) have been associated mostly with early onset epileptic encephalopathies (EOEEs) and Ohtahara syndrome, with a mutation detection...
Epilepsia - issue: 12 - volume: 56 - pages: 1931-1940.

Grozeva, D.  et al. 2015

Targeted Next-Generation Sequencing Analysis of 1,000 Individuals with Intellectual Disability

To identify genetic causes of intellectual disability (ID), we screened a cohort of 986 individuals with moderate to severe ID for variants in 565 known or candidate ID-associated genes using targeted...
Hum. Mutat. - issue: 12 - volume: 36 - pages: 1197-1204.

Chanson, P.  et al. 2015

Pegvisomant treatment in patients with acromegaly in clinical practice: The French ACROSTUDY

OBJECTIVE: To monitor long-term pegvisomant treatment of patients with acromegaly in routine clinical practice. PATIENTS AND METHODS: The French ACROSTUDY is part of the global ACROSTUDY, an...
Ann. Endocrinol. (Paris) - issue: 6 - volume: 76 - pages: 664-670.

Pleil, A.  et al. 2015

Development of a Prediction Model of Disease Activity in Support of Clinical Practice - the Acrodat Experience


Value Health - issue: 7 - volume: 18 - pages: A708.

Milh, M.  et al. 2015

Variable clinical expression in patients with mosaicism for KCNQ2 mutations

Mutations in the KCNQ2 gene, encoding a potassium channel subunit, were reported in patients presenting epileptic phenotypes of varying severity. Patients affected by benign familial neonatal epilepsy...
Am. J. Med. Genet. A - issue: 10 - volume: 167A - pages: 2314-2318.

Castinetti, F.  et al. 2015

ISL1 Is Necessary for Maximal Thyrotrope Response to Hypothyroidism

ISLET1 is a homeodomain transcription factor necessary for development of the pituitary, retina, motor neurons, heart, and pancreas. Isl1-deficient mice (Isl1(-/-)) die early during embryogenesis at...
Mol. Endocrinol. - issue: 10 - volume: 29 - pages: 1510-1521.

Doummar, D.  et al. 2015

A Novel Homozygous TBC1D24 Mutation Causing Multifocal Myoclonus With Cerebellar Involvement


Mov. Disord. - issue: 10 - volume: 30 - pages: 1431-1432.

Abidi, A.  et al. 2015

A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels

Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the...
Neurobiol. Dis. - issue: - volume: 80 - pages: 80-92.

Abidi, A.  et al. 2015

A recurrent KCNQ2 pore mutation causing early onset epileptic encephalopathy has a moderate effect on M current but alters subcellular localization of Kv7 channels

Mutations in the KCNQ2 gene encoding the voltage-dependent potassium M channel Kv7.2 subunit cause either benign epilepsy or early onset epileptic encephalopathy (EOEE). It has been proposed that the...
Neurobiol. Dis. - issue: - volume: 80 - pages: 80-92.

El Waly, B.  et al. 2015

Nhej1 Deficiency Causes Abnormal Development of the Cerebral Cortex

DNA double-strand breaks (DSBs) frequently occur in rapidly dividing cells such as proliferating progenitors during central nervous system development. If they cannot be repaired, these lesions will...
Mol. Neurobiol. - issue: 1 - volume: 52 - pages: 771-782.

Le Marc'hadour, P.  et al. 2015

Postoperative follow-up of Cushing's disease using cortisol, desmopressin and coupled dexamethasone-desmopressin tests: a head-to-head comparison

OBJECTIVE: Predicting the outcome of patients operated on for Cushing's disease (CD) is a challenging task. Our objective was to assess the accuracy of immediate postsurgical plasma cortisol,...
Clin. Endocrinol. (Oxf) - issue: 2 - volume: 83 - pages: 216-222.

Abidi, A.  et al. 2015

Early-onset epileptic encephalopathy as the initial clinical presentation of WDR45 deletion in a male patient

Variants in the WD repeat 45 (WDR45) gene in human Xp11.23 have recently been identified in patients suffering from neurodegeneration with brain iron accumulation, a genetically and phenotypically...
Eur. J. Hum. Genet. - issue: - volume: - pages: .

Petersenn, S.  et al. 2015

Therapy of endocrine disease: outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

OBJECTIVE: A number of factors can influence the reported outcomes of transsphenoidal surgery (TSS) for Cushing's disease - including different remission and recurrence criteria, for which there is no...
Eur. J. Endocrinol. - issue: 6 - volume: 172 - pages: R227-239.

Bouvattier, C.  et al. 2015

Clinical Outcome, Hormonal Status, Gonadotrope Axis, and Testicular Function in 219 Adult Men Born With Classic 21-Hydroxylase Deficiency. A French National Survey

CONTEXT: Outcomes of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women, but less so in men. OBJECTIVE: The objective was to...
J. Clin. Endocrinol. Metab. - issue: 6 - volume: 100 - pages: 2303-2313.

Niceta, M.  et al. 2015

Mutations Impairing GSK3-Mediated MAF Phosphorylation Cause Cataract, Deafness, Intellectual Disability, Seizures, and a Down Syndrome-like Facies

Transcription factors operate in developmental processes to mediate inductive events and cell competence, and perturbation of their function or regulation can dramatically affect morphogenesis,...
Am. J. Hum. Genet. - issue: 5 - volume: 96 - pages: 816-825.

Nissenkorn, A.  et al. 2015

Epilepsy in Rett syndrome-Lessons from the Rett networked database

ObjectiveRett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and...
Epilepsia - issue: 4 - volume: 56 - pages: 569-576.

Nissenkorn, A.  et al. 2015

Epilepsy in Rett syndrome--lessons from the Rett networked database

OBJECTIVE: Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and...
Epilepsia - issue: 4 - volume: 56 - pages: 569-576.

Potorac, I.  et al. 2015

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive...
Endocr. Relat. Cancer - issue: 2 - volume: 22 - pages: 169-177.

Poulat, A.  et al. 2015

Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability

Mutations in the TBC1D24 gene were first reported in an Italian family with a unique epileptic phenotype consisting of drug-responsive, early-onset idiopathic myoclonic seizures. Patients presented...
Epilepsy Res. - issue: - volume: 111 - pages: 72-77.

Poulat, A.  et al. 2015

Homozygous TBC1D24 mutation in two siblings with familial infantile myoclonic epilepsy (FIME) and moderate intellectual disability

Mutations in the TBC1D24 gene were first reported in an Italian family with a unique epileptic phenotype consisting of drug-responsive, early-onset idiopathic myoclonic seizures. Patients presented...
Epilepsy Res. - issue: - volume: 111 - pages: 72-77.

Bauer, M.  et al. 2015

Infectious and Immunologic Phenotype of MECP2 Duplication Syndrome

MECP2 (methyl CpG binding protein 2) duplication causes syndromic intellectual disability. Patients often suffer from life-threatening infections, suggesting an additional immunodeficiency. We...
J. Clin. Immunol. - issue: 2 - volume: 35 - pages: 168-181.

Castinetti, F.  et al. 2015

An observational study on adrenal insufficiency in a French tertiary centre: Real life versus theory

BACKGROUND: Patients suffering from adrenal insufficiency, whether primary (PAI) or secondary (SAI) have an increased mortality risk and increased morbidity. There are no guidelines on hydrocortisone...
Ann. Endocrinol. (Paris) - issue: 1 - volume: 76 - pages: 1-8.

Albarel, F.  et al. 2015

Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma

OBJECTIVE: Few data are published on the long-term follow-up of ipilimumab-induced hypophysitis, a cytotoxic T-lymphocyte antigen 4 antibody. We characterized hypophysitis in terms of clinical signs,...
Eur. J. Endocrinol. - issue: 2 - volume: 172 - pages: 195-204.

Castinetti, F.  et al. 2015

Combined pituitary hormone deficiency: current and future status

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a...
J. Endocrinol. Invest. - issue: 1 - volume: 38 - pages: 1-12.

El-Khoury, R.  et al. 2014

GABA and glutamate pathways are spatially and developmentally affected in the brain of Mecp2-deficient mice

Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT)...
PLoS ONE - issue: 3 - volume: 9 - pages: e92169.

Brue, T.  et al. 2014

Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies

BACKGROUND: DAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with...
BMC Med. Genet. - issue: - volume: 15 - pages: 139.

Herbaux, C.  et al. 2014

Incidence of Atrx Mutations in Myelodysplastic Syndromes (MDS)

WOS:000349242701174
Blood - issue: 21 - volume: 124 - pages: .

Mear, Y.  et al. 2014

Ghrelin receptor (GHS-R1a) and its constitutive activity in somatotroph adenomas: a new co-targeting therapy using GHS-R1a inverse agonists and somatostatin analogs

CONTEXT: The ghrelin receptor GHS-R1a is highly expressed in human somatotroph adenomas and exhibits unusually high basal signaling activity. In humans, the suppression of this constitutive activity...
J. Clin. Endocrinol. Metab. - issue: 12 - volume: 99 - pages: E2463-2471.

Lacoste, C.  et al. 2014

Mutations of codon 2085 in the helicase domain of ATRX are recurrent and cause ATRX syndrome

WOS:000344004800017
Clin. Genet. - issue: 5 - volume: 86 - pages: 502-503.

Gorincour, G.  et al. 2014

Fetal skeletal computed tomography: When? How? Why?

Purpose: To study the additional role of fetal skeletal computed tomography in suspected prenatal bone abnormalities. Materials and methods: Two centers included in a retrospective study all fetuses...
Diagn. Interv. Imaging - issue: 11 - volume: 95 - pages: 1045-1053.

Gadelha, MR.  et al. 2014

Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial

BACKGROUND: Many patients with acromegaly do not achieve biochemical control despite receiving high doses of the first-generation somatostatin analogues octreotide or lanreotide. In the PAOLA trial,...
Lancet Diabetes Endocrinol - issue: 11 - volume: 2 - pages: 875-884.

Mohamed, A.  et al. 2014

Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) raise difficult therapeutic problems despite the emergence of targeted therapies. Somatostatin analogs (SSA) remain pivotal therapeutic drugs....
Endocr. Relat. Cancer - issue: 5 - volume: 21 - pages: 691-704.

Poulton, CJ.  et al. 2014

Severe presentation of WDR62 mutation: is there a role for modifying genetic factors?

Mutations in WDR62 are associated with primary microcephaly; however, they have been reported with wide phenotypic variability. We report on six individuals with novel WDR62 mutations who illustrate...
Am. J. Med. Genet. A - issue: 9 - volume: 164A - pages: 2161-2171.

Pivonello, R.  et al. 2014

Pasireotide treatment significantly improves clinical signs and symptoms in patients with Cushing's disease: results from a Phase III study

OBJECTIVE: Signs and symptoms of Cushing's disease are associated with high burden of illness. In this analysis, we evaluated the effect of pasireotide treatment on signs and symptoms in patients with...
Clin. Endocrinol. (Oxf) - issue: 3 - volume: 81 - pages: 408-417.

Bakiri, F.  et al. 2014

Pituitary apoplexy after somatostatin analogue administration: coincidental or causative?


Clin. Endocrinol. (Oxf) - issue: 3 - volume: 81 - pages: 471-473.

Mignon-Ravix, C.  et al. 2014

Intragenic Rearrangements in X-Linked Intellectual Deficiency: Results of a-CGH in a Series of 54 Patients and Identification of TRPC5 and KLHL15 As Potential XLID Genes

High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the...
Am. J. Med. Genet. A - issue: 8 - volume: 164 - pages: 1991-1997.

Mignon-Ravix, C.  et al. 2014

Intragenic rearrangements in X-linked intellectual deficiency: results of a-CGH in a series of 54 patients and identification of TRPC5 and KLHL15 as potential XLID genes

High-resolution array comparative genomic hybridization (a-CGH) enables the detection of intragenic rearrangements, such as single exon deletion or duplication. This approach can lead to the...
Am. J. Med. Genet. A - issue: 8 - volume: 164A - pages: 1991-1997.

Thevenon, J.  et al. 2014

Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life

Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay,...
Am. J. Hum. Genet. - issue: 1 - volume: 95 - pages: 113-120.

Thevenon, J.  et al. 2014

Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life

Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay,...
Am. J. Hum. Genet. - issue: 1 - volume: 95 - pages: 113-120.

Nozières, C.  et al. 2014

p.Ala541Thr variant of MEN1 gene: a non deleterious polymorphism or a pathogenic mutation?

CONTEXT: Multiple Endocrine Neoplasia Type 1 (MEN1) is an autosomal dominant inherited syndrome, related to mutations in the MEN1 gene. Controversial data suggest that the nonsynonymous p.Ala541Thr...
Ann. Endocrinol. (Paris) - issue: 3 - volume: 75 - pages: 133-140.

Abdi, L.  et al. 2014

A monocentric experience of growth hormone replacement therapy in adult patients

OBJECTIVES: To describe the results of growth hormone (GH) therapy in adult GH-deficient patients treated in a tertiary referral center, with a focus on quality of life and adherence. PATIENTS AND...
Ann. Endocrinol. (Paris) - issue: 3 - volume: 75 - pages: 176-183.

Philippon, M.  et al. 2014

Bilateral neck exploration in patients with primary hyperparathyroidism and discordant imaging results: a single-centre study

INTRODUCTION: Focused parathyroidectomy is the treatment of choice for patients with concordant positive imaging. Bilateral cervical exploration is performed for cases with discordant imaging, yet...
Eur. J. Endocrinol. - issue: 5 - volume: 170 - pages: 719-725.

Castinetti, F.  et al. 2014

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to...
Lancet Oncol. - issue: 6 - volume: 15 - pages: 648-655.

Castinetti, F.  et al. 2014

Ketoconazole in Cushing's disease: is it worth a try?

BACKGROUND: The use of ketoconazole has been recently questioned after warnings from the European Medicine Agencies and the Food and Drug Administration due to potential hepatotoxicity. However,...
J. Clin. Endocrinol. Metab. - issue: 5 - volume: 99 - pages: 1623-1630.

Tardy-Guidollet, V.  et al. 2014

New Management Strategy of Pregnancies at Risk of Congenital Adrenal Hyperplasia Using Fetal Sex Determination in Maternal Serum: French Cohort of 258 Cases (2002-2011)

Context: Prenatal dexamethasone (DEX) treatment has been proposed since 1984 to prevent genital virilization in girls with congenital adrenal hyperplasia (CAH). DEX is effective in CAH females if...
J. Clin. Endocrinol. Metab. - issue: 4 - volume: 99 - pages: 1180-1188.

Caron, PJ.  et al. 2014

Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial

CONTEXT: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the...
J. Clin. Endocrinol. Metab. - issue: 4 - volume: 99 - pages: 1282-1290.

El-Khoury, R.  et al. 2014

GABA and Glutamate Pathways Are Spatially and Developmentally Affected in the Brain of Mecp2-Deficient Mice

Proper brain functioning requires a fine-tuning between excitatory and inhibitory neurotransmission, a balance maintained through the regulation and release of glutamate and GABA. Rett syndrome (RTT)...
PLoS One - issue: 3 - volume: 9 - pages: e92169.

Cacciagli, P.  et al. 2014

AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker...
Eur. J. Hum. Genet. - issue: 3 - volume: 22 - pages: 363-368.

Cacciagli, P.  et al. 2014

AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome)

MRXS5 or Pettigrew syndrome was described 20 years ago in a four generation family including nine affected individuals presenting with facial dysmorphism, intellectual disability, Dandy-Walker...
Eur. J. Hum. Genet. - issue: 3 - volume: 22 - pages: 363-368.

Colao, A.  et al. 2014

Pasireotide versus octreotide in acromegaly: a head-to-head superiority study

CONTEXT: Biochemical control reduces morbidity and increases life expectancy in patients with acromegaly. With current medical therapies, including the gold standard octreotide long-acting-release...
J. Clin. Endocrinol. Metab. - issue: 3 - volume: 99 - pages: 791-799.

Becquet, D.  et al. 2014

Evidence for an internal and functional circadian clock in rat pituitary cells

In primary cultures of rat pituitary cells and in a pituitary sommatolactotroph cell line (GH4C1), endogenous core-clock- as well as hormone-genes such as prolactin displayed a rhythmic expression...
Mol. Cell. Endocrinol. - issue: 2 - volume: 382 - pages: 888-898.

Petersenn, S.  et al. 2014

High variability in baseline urinary free cortisol values in patients with Cushing's disease

OBJECTIVE: Twenty-four-hour urinary free cortisol (UFC) sampling is commonly used to evaluate Cushing's syndrome. Because there are few data on UFC variability in patients with active Cushing's...
Clin. Endocrinol. (Oxf) - issue: 2 - volume: 80 - pages: 261-269.

Maione, L.  et al. 2013

R31C GNRH1 mutation and congenital hypogonadotropic hypogonadism

Normosmic congenital hypogonadotropic hypogonadism (nCHH) is a rare reproductive disease leading to lack of puberty and infertility. Loss-of-function mutations of GNRH1 gene are a very rare cause of...
PLoS ONE - issue: 7 - volume: 8 - pages: e69616.

Kaddoum, L.  et al. 2013

Isoform-specific anti-MeCP2 antibodies confirm that expression of the e1 isoform strongly predominates in the brain

Rett syndrome is a neurological disorder caused by mutations in the MECP2 gene.  MeCP2 transcripts are alternatively spliced to generate two protein isoforms (MeCP2_e1 and MeCP2_e2) that differ at...
F1000Res - issue: - volume: 2 - pages: 204.

Cordier, C.  et al. 2013

French Professionals in Genetic Counselor Careers

The profession of genetic counseling in France was recognized in 2004, based on the recommendations of a mandate commissioned by the Health Minister to explore the medical demographics of France. The...
J. Genet. Couns. - issue: 6 - volume: 22 - pages: 844-848.

Tanyalcin, I.  et al. 2013

Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: Case study and literature review

Background: The BIG2 protein, coded by ARFGEF2 indirectly assists neuronal proliferation and migration during cortical development. Mutations in ARFGEF2 have been reported as a rare cause of...
Eur. J. Paediatr. Neurol. - issue: 6 - volume: 17 - pages: 666-670.

Tanyalçin, I.  et al. 2013

Elaborating the phenotypic spectrum associated with mutations in ARFGEF2: case study and literature review

BACKGROUND: The BIG2 protein, coded by ARFGEF2 indirectly assists neuronal proliferation and migration during cortical development. Mutations in ARFGEF2 have been reported as a rare cause of...
Eur. J. Paediatr. Neurol. - issue: 6 - volume: 17 - pages: 666-670.

Michot, C.  et al. 2013

Finger creases lend a hand in Kabuki syndrome

Kabuki syndrome (KS) is a rare syndrome associating malformations with intellectual deficiency and numerous visceral, orthopedic, endocrinological, immune and autoimmune complications. The early...
Eur. J. Med. Genet. - issue: 10 - volume: 56 - pages: 556-560.

Sanchez-Mut, JV.  et al. 2013

DNA methylation map of mouse and human brain identifies target genes in Alzheimer's disease

The central nervous system has a pattern of gene expression that is closely regulated with respect to functional and anatomical regions. DNA methylation is a major regulator of transcriptional...
Brain - issue: Pt 10 - volume: 136 - pages: 3018-3027.

Cacciagli, P.  et al. 2013

Mutations in BCAP31 Cause a Severe X-Linked Phenotype with Deafness, Dystonia, and Central Hypomyelination and Disorganize the Golgi Apparatus

BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to...
Am. J. Hum. Genet. - issue: 3 - volume: 93 - pages: 579-586.

Cacciagli, P.  et al. 2013

Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia, and central hypomyelination and disorganize the Golgi apparatus

BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins. It is a chaperone protein involved in several pathways, including ER-associated degradation, export of ER proteins to...
Am. J. Hum. Genet. - issue: 3 - volume: 93 - pages: 579-586.

Van Maldergem, L.  et al. 2013

Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth

Existence of a discrete new X-linked intellectual disability (XLID) syndrome due to KIAA2022 deficiency was questioned by disruption of KIAA2022 by an X-chromosome pericentric inversion in a XLID...
Hum. Mol. Genet. - issue: 16 - volume: 22 - pages: 3306-3314.

Van Maldergem, L.  et al. 2013

Loss of function of KIAA2022 causes mild to severe intellectual disability with an autism spectrum disorder and impairs neurite outgrowth

Existence of a discrete new X-linked intellectual disability (XLID) syndrome due to KIAA2022 deficiency was questioned by disruption of KIAA2022 by an X-chromosome pericentric inversion in a XLID...
Hum. Mol. Genet. - issue: 16 - volume: 22 - pages: 3306-3314.

Milh, M.  et al. 2013

Novel compound heterozygous mutations in TBC1D24 cause familial malignant migrating partial seizures of infancy

Early-onset epileptic encephalopathies (EOEEs) are a group of rare devastating epileptic syndromes of infancy characterized by severe drug-resistant seizures and electroencephalographic abnormalities....
Hum. Mutat. - issue: 6 - volume: 34 - pages: 869-872.

Milh, M.  et al. 2013

Similar early characteristics but variable neurological outcome of patients with a de novo mutation of KCNQ2

BACKGROUND: Early onset epileptic encephalopathies (EOEEs) are dramatic heterogeneous conditions in which aetiology, seizures and/or interictal EEG have a negative impact on neurological development....
Orphanet J Rare Dis - issue: - volume: 8 - pages: 80.

Popovici, C.  et al. 2013

Mosaic 15q13.3 deletion including CHRNA7 gene in monozygotic twins

Deletions in 15q13.3 belong to the most frequently identified recurrent CNVs, and lead to mental retardation, seizures and minor dysmorphism. We report on two monozygotic twin boys with a mosaic 1.5...
Eur. J. Med. Genet. - issue: 5 - volume: 56 - pages: 274-277.

Cuny, T.  et al. 2013

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

CONTEXT: Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) have been identified in young patients (age ≤30 years old) with sporadic pituitary macroadenomas. Otherwise,...
Eur. J. Endocrinol. - issue: 4 - volume: 168 - pages: 533-541.

Delio, M.  et al. 2013

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic...
Am. J. Hum. Genet. - issue: 3 - volume: 92 - pages: 439-447.

Albarel, F.  et al. 2013

Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients

INTRODUCTION: Given the new therapeutic options in acromegaly, it seemed important to evaluate the outcome of operated acromegalic patients today. OBJECTIVE: To analyse the characteristics and short-...
Clin. Endocrinol. (Oxf) - issue: 2 - volume: 78 - pages: 263-270.

Lamine, F.  et al. 2012

Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best...
Pituitary - issue: - volume: 15 Suppl 1 - pages: S81-86.

Budry, L.  et al. 2012

The selector gene Pax7 dictates alternate pituitary cell fates through its pioneer action on chromatin remodeling

The anterior and intermediate lobes of the pituitary gland derive from the surface ectoderm. They provide a simple system to assess mechanisms of developmental identity established by tissue...
Genes Dev. - issue: 20 - volume: 26 - pages: 2299-2310.

Langrand, C.  et al. 2012

Hypothalamo-pituitary sarcoidosis: a multicenter study of 24 patients

AIM: To assess clinical features, treatment and outcome of Hypothalamo-pituitary (HP) sarcoidosis and to determine whether HP is associated with a particular clinical phenotype of sarcoidosis. DESIGN:...
QJM - issue: 10 - volume: 105 - pages: 981-995.

Bachelot, A.  et al. 2012

Influence of hormonal control on LH pulsatility and secretion in women with classical congenital adrenal hyperplasia

OBJECTIVE: Women with classical congenital adrenal hyperplasia (CAH) exhibit reduced fertility due to several factors including anovulation. This has been attributed to a disturbed gonadotropic axis...
Eur. J. Endocrinol. - issue: 4 - volume: 167 - pages: 499-505.

Grillo, E.  et al. 2012

Rett networked database: an integrated clinical and genetic network of Rett syndrome databases

Rett syndrome (RTT) is a neurodevelopmental disorder with one principal phenotype and several distinct, atypical variants (Zappella, early seizure onset and congenital variants). Mutations in MECP2...
Hum. Mutat. - issue: 7 - volume: 33 - pages: 1031-1036.

Roux, J.  et al. 2012

Modification of Mecp2 dosage alters axonal transport through the Huntingtin/Hap1 pathway

Mecp2 deficiency or overexpression causes a wide spectrum of neurological diseases in humans among which Rett Syndrome is the prototype. Pathogenic mechanisms are thought to involve transcriptional...
Neurobiol. Dis. - issue: 2 - volume: 45 - pages: 786-795.

Roux, J.  et al. 2012

Modification of Mecp2 dosage alters axonal transport through the Huntingtin/Hap1 pathway

Mecp2 deficiency or overexpression causes a wide spectrum of neurological diseases in humans among which Rett Syndrome is the prototype. Pathogenic mechanisms are thought to involve transcriptional...
Neurobiol. Dis. - issue: 2 - volume: 45 - pages: 786-795.

Roux, J.  et al. 2012

[Unexpected link between Huntington disease and Rett syndrome]


Med Sci (Paris) - issue: 1 - volume: 28 - pages: 44-46.

Milh, M.  et al. 2011

Epileptic and nonepileptic features in patients with early onset epileptic encephalopathy and STXBP1 mutations

PURPOSE: STXBP1 (MUNC18-1) mutations have been associated with various types of epilepsies, mostly beginning early in life. To refine the phenotype associated with STXBP1 aberrations in early onset...
Epilepsia - issue: 10 - volume: 52 - pages: 1828-1834.

Panayotis, N.  et al. 2011

Biogenic amines and their metabolites are differentially affected in the Mecp2-deficient mouse brain

BACKGROUND: Rett syndrome (RTT, MIM #312750) is a severe neurological disorder caused by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Female patients are affected with an...
BMC Neurosci - issue: - volume: 12 - pages: 47.

Mégarbané, A.  et al. 2011

Ambiguous genitalia, microcephaly, seizures, bone malformations, and early death: a distinct MCA/MR syndrome

We report on two siblings with hypotonia, ambiguous genitalia, microcephaly, ptosis, microretrognathia, thin lips, seizures, absent ossification of pubic rami, and brain abnormalities at the MRI. The...
Am. J. Med. Genet. A - issue: 5 - volume: 155A - pages: 1147-1151.

Ravel, A.  et al. 2011

How many entities exist for the spectrum of disorders associated with brachydactyly, syndactyly, short stature, microcephaly, and intellectual disability?

We describe a French young man with digital anomalies consisting of brachydactyly, F1-5 bilateral camptodactyly, interdigital webbing, F5 bilateral radial clinodactyly, and partial syndactyly of some...
Am. J. Med. Genet. A - issue: 4 - volume: 155A - pages: 880-884.

Panayotis, N.  et al. 2011

Morphological and functional alterations in the substantia nigra pars compacta of the Mecp2-null mouse

Rett syndrome (RTT) is a severe neurological disorder caused by mutations in the MECP2 gene, in which older patients often develop parkinsonian features. Although Mecp2 has been shown to modulate the...
Neurobiol. Dis. - issue: 2 - volume: 41 - pages: 385-397.

Pratte, M.  et al. 2011

Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice

The methyl-CpG binding protein 2 (Mecp2) gene encodes a nuclear transcriptional modulator highly expressed in post-mitotic neurons. Mutations of this gene cause a large spectrum of neurological...
Behav. Brain Res. - issue: 1 - volume: 216 - pages: 313-320.

Neul, JL.  et al. 2010

Rett syndrome: revised diagnostic criteria and nomenclature

OBJECTIVE: Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2...
Ann. Neurol. - issue: 6 - volume: 68 - pages: 944-950.

Cacciagli, P.  et al. 2010

Disruption of the ATP8A2 gene in a patient with a t(10;13) de novo balanced translocation and a severe neurological phenotype

Mental retardation is a frequent condition that is clinically and genetically highly heterogeneous. One of the strategies used to identify new causative genes is to take advantage of balanced...
Eur. J. Hum. Genet. - issue: 12 - volume: 18 - pages: 1360-1363.

Endele, S.  et al. 2010

Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes

N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly...
Nat. Genet. - issue: 11 - volume: 42 - pages: 1021-1026.

Bahi-Buisson, N.  et al. 2010

GPR56-related bilateral frontoparietal polymicrogyria: further evidence for an overlap with the cobblestone complex

GPR56 mutations cause an autosomal recessive polymicrogyria syndrome that has distinctive radiological features combining bilateral frontoparietal polymicrogyria, white matter abnormalities and...
Brain - issue: 11 - volume: 133 - pages: 3194-3209.

Roux, J.  et al. 2010

Progressive noradrenergic deficits in the locus coeruleus of Mecp2 deficient mice

Methyl-CpG binding protein 2 (MeCP2) is a transcriptional regulator. Mutations in this gene cause a wide range of neurological disorders. Mecp2 deficiency has been previously associated to...
J. Neurosci. Res. - issue: 7 - volume: 88 - pages: 1500-1509.

Thienpont, B.  et al. 2010

Duplications of the critical Rubinstein-Taybi deletion region on chromosome 16p13.3 cause a novel recognisable syndrome

BACKGROUND: The introduction of molecular karyotyping technologies facilitated the identification of specific genetic disorders associated with imbalances of certain genomic regions. A detailed...
J. Med. Genet. - issue: 3 - volume: 47 - pages: 155-161.

Mignon-Ravix, C.  et al. 2010

Deletion of YWHAE in a patient with periventricular heterotopias and pronounced corpus callosum hypoplasia

BACKGROUND: Malformations of cortical development are not rare and cause a wide spectrum of neurological diseases based on the affected region in the cerebral cortex. A significant proportion of these...
J. Med. Genet. - issue: 2 - volume: 47 - pages: 132-136.

Roux, J.  et al. 2010

Biogenic amines in Rett syndrome: the usual suspects

Rett syndrome (RTT) is a severe postnatal neurological disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. In affected children, most biological parameters, including brain...
Behav. Genet. - issue: 1 - volume: 40 - pages: 59-75.

Mencarelli, MA.  et al. 2010

Novel FOXG1 mutations associated with the congenital variant of Rett syndrome

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder representing one of the most common genetic causes of mental retardation in girls. The classic form is caused by MECP2 mutations. In...
J. Med. Genet. - issue: 1 - volume: 47 - pages: 49-53.

Solé, G.  et al. 2009

Bilateral periventricular nodular heterotopia in France: frequency of mutations in FLNA, phenotypic heterogeneity and spectrum of mutations

Bilateral periventricular nodular heterotopia (BPNH) is the most common form of periventricular heterotopia. Mutations in FLNA, encoding filamin A, are responsible for the X linked dominant form of...
J. Neurol. Neurosurg. Psychiatry - issue: 12 - volume: 80 - pages: 1394-1398.

Cantagrel, V.  et al. 2009

Spatiotemporal expression in mouse brain of Kiaa2022, a gene disrupted in two patients with severe mental retardation

We previously identified an inactivating disruption of the X-linked KIAA2022 gene by a chromosomal rearrangement in two male patients with severe mental retardation. In order to determine if KIAA2022...
Gene Expr. Patterns - issue: 6 - volume: 9 - pages: 423-429.

Haddad, M.  et al. 2009

Characterization of a de novo balanced translocation in a patient with moderate mental retardation and dysmorphic features

Moderate mental retardation (MR) could affect up to 3% of the general population. A proportion of these cases has a genetic origin. Genes responsible for mental retardation can be identified taking...
Eur J Med Genet - issue: 4 - volume: 52 - pages: 211-217.

Cardoso, C.  et al. 2009

Periventricular heterotopia, mental retardation, and epilepsy associated with 5q14.3-q15 deletion

BACKGROUND: Periventricular heterotopia (PH) is an etiologically heterogeneous disorder characterized by nodules of neurons ectopically placed along the lateral ventricles. Most affected patients have...
Neurology - issue: 9 - volume: 72 - pages: 784-792.

Roux, J.  et al. 2008

Tyrosine hydroxylase deficit in the chemoafferent and the sympathoadrenergic pathways of the Mecp2 deficient mouse

Mutations in the gene encoding the transcriptional methyl-CpG binding protein 2 (Mecp2) cause a wide range of neurological disorders and the better known of these diseases is Rett syndrome (RS). Mecp2...
Neurosci. Lett. - issue: 1 - volume: 447 - pages: 82-86.

Giurgea, I.  et al. 2008

TCF4 deletions in Pitt-Hopkins Syndrome

Pitt-Hopkins syndrome (PHS) is a probably underdiagnosed, syndromic mental retardation disorder, marked by hyperventilation episodes and characteristic dysmorphism (large beaked nose, wide mouth,...
Hum. Mutat. - issue: 11 - volume: 29 - pages: E242-251.

Dura, E.  et al. 2008

Expression of methyl CpG binding protein 2 (Mecp2) during the postnatal development of the mouse brainstem

Methyl CpG binding protein 2 (MeCP2) is a member of the methylated DNA binding protein family able to modulate the transcription of target genes. Mutations in MECP2 lead to a wide range of...
Brain Res. - issue: - volume: 1236 - pages: 176-184.

Bahi-Buisson, N.  et al. 2008

Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations

OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we...
J. Med. Genet. - issue: 10 - volume: 45 - pages: 647-653.

Viola, A.  et al. 2007

Metabolic fingerprints of altered brain growth, osmoregulation and neurotransmission in a Rett syndrome model

BACKGROUND: Rett syndrome (RS) is the leading cause of profound mental retardation of genetic origin in girls. Since RS is mostly caused by mutations in the MECP2 gene, transgenic animal models such...
PLoS ONE - issue: 1 - volume: 2 - pages: e157.

Moncla, A.  et al. 2007

A cluster of translocation breakpoints in 2q37 is associated with overexpression of NPPC in patients with a similar overgrowth phenotype

Overexpression of the C-type natriuretic peptide, encoded by the NPPC gene in 2q37.1, was recently reported in a patient presenting an overgrowth phenotype and a balanced t(2;7)(q37.1;q21.3)...
Hum. Mutat. - issue: 12 - volume: 28 - pages: 1183-1188.

Roux, J.  et al. 2007

[Pharmacological treatment of Rett syndrome improves breathing and survival in a mouse model]


Med Sci (Paris) - issue: 10 - volume: 23 - pages: 805-807.

Villard, L.  et al. 2007

MECP2 mutations in males

Rett syndrome (RS; MIM 312750) is a severe neurological disorder affecting exclusively females. Its prevalence is about 1 in 10,000 female births, and it is a prominent cause of profound mental...
J. Med. Genet. - issue: 7 - volume: 44 - pages: 417-423.

Cantagrel, V.  et al. 2007

Truncation of NHEJ1 in a patient with polymicrogyria

Polymicrogyria (PMG) is a common malformation of the human cerebral cortex for which both acquired and genetic causes are known. Although genetic heterogeneity is documented, only one gene is...
Hum. Mutat. - issue: 4 - volume: 28 - pages: 356-364.

Roux, J.  et al. 2007

Treatment with desipramine improves breathing and survival in a mouse model for Rett syndrome

Rett syndrome (RS) is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein2 (MECP2) gene. No effective treatment exists. We previously showed...
Eur. J. Neurosci. - issue: 7 - volume: 25 - pages: 1915-1922.

Bienvenu, T.  et al. 2006

The incidence of Rett syndrome in France

Since the description of Rett syndrome, only a handful of epidemiologic studies based only on clinical investigation have been reported. Mutations in the MECP2 gene are associated with Rett syndrome...
Pediatr. Neurol. - issue: 5 - volume: 34 - pages: 372-375.

Saywell, V.  et al. 2006

Brain magnetic resonance study of Mecp2 deletion effects on anatomy and metabolism

Rett syndrome, a neurodevelopmental X-linked disorder, represents the most important genetic cause of severe mental retardation in the female population and results from a mutation in the gene...
Biochem. Biophys. Res. Commun. - issue: 3 - volume: 340 - pages: 776-783.

Philippe, C.  et al. 2006

Spectrum and distribution of MECP2 mutations in 424 Rett syndrome patients: a molecular update

Mutations in the MECP2 (Methyl-CpG-binding protein) gene have been reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. Recent studies have identified large gene...
Eur J Med Genet - issue: 1 - volume: 49 - pages: 9-18.

Villard, L.  et al. 2006

[Noradrenaline deficiency as the origin of respiratory disorders in Rett syndrome an animal model]


Med Sci (Paris) - issue: 1 - volume: 22 - pages: 81-83.

Iurov, II.  et al. 2005

[Epigenetic study of Rett's syndrome as an adequate model for autistic disorders]

Rett's syndrome (RTT) is a severe hereditary disorder of the nervous system. MECP2 gene mutations are considered as a primary cause of the disease. In the present study, we have found MECP2 mutations...
Zh Nevrol Psikhiatr Im S S Korsakova - issue: 7 - volume: 105 - pages: 4-11.

Viemari, J.  et al. 2005

Mecp2 deficiency disrupts norepinephrine and respiratory systems in mice

Rett syndrome is a severe X-linked neurological disorder in which most patients have mutations in the methyl-CpG binding protein 2 (MECP2) gene and suffer from bioaminergic deficiencies and...
J. Neurosci. - issue: 50 - volume: 25 - pages: 11521-11530.

Chabrol, B.  et al. 2005

Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families

Recent reports have demonstrated that mutations in the OPHN1 gene were responsible for a syndromic rather than non-specific mental retardation. Abnormalities of the posterior fossa with cerebellar...
Am. J. Med. Genet. A - issue: 4 - volume: 138 - pages: 314-317.

Lower, KM.  et al. 2004

Partial androgen insensitivity syndrome and t(X;5): are there upstream regulatory elements of the androgen receptor gene?

BACKGROUND/AIMS: Two half-brothers with similar malformed genitals, who both inherited a maternally derived t(X;5)(q13;p15) translocation, have a phenotype consistent with partial androgen sensitivity...
Horm. Res. - issue: 4 - volume: 62 - pages: 208-214.

Cantagrel, V.  et al. 2004

Disruption of a new X linked gene highly expressed in brain in a family with two mentally retarded males

BACKGROUND: Mental retardation (MR) affects 2-3% of the human population and some of these cases are genetically determined. Although several genes responsible for MR have been identified, many cases...
J. Med. Genet. - issue: 10 - volume: 41 - pages: 736-742.

Philip, N.  et al. 2003

Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia


J. Med. Genet. - issue: 6 - volume: 40 - pages: 441-446.

Vorsanova, SG.  et al. 2002

[Genotype-phenotype correlations in Rett syndrome: the study of Russian cohort of patients]

Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein 2 gene (MECP2). We carried out a mutations analysis in Russian cohort of patients with...
Zh Nevrol Psikhiatr Im S S Korsakova - issue: 10 - volume: 102 - pages: 23-29.

Bienvenu, T.  et al. 2002

Spectrum of MECP2 mutations in Rett syndrome

Mutations in the MECP2 (Methyl-CpG-binding protein) gene recently have been reported to cause Rett syndrome (RTT), an X-linked progressive encephalopathy. We have collected the results of MECP2...
Genet. Test. - issue: 1 - volume: 6 - pages: 1-6.

Braybrook, C.  et al. 2002

Craniofacial expression of human and murine TBX22 correlates with the cleft palate and ankyloglossia phenotype observed in CPX patients

Cleft palate with ankyloglossia (CPX; MIM 303400) is inherited as a Mendelian, semidominant X-linked disorder and has been described in several large families from different ethnic origins. It is a...
Hum. Mol. Genet. - issue: 22 - volume: 11 - pages: 2793-2804.

Villard, L.  et al. 2002

Alpha-thalassemia/mental retardation syndrome, X-Linked (ATR-X, MIM #301040, ATR-X/XNP/XH2 gene MIM #300032)


Eur. J. Hum. Genet. - issue: 4 - volume: 10 - pages: 223-225.

Villard, L.  et al. 2002

A locus for bilateral perisylvian polymicrogyria maps to Xq28

Polymicrogyria (PMG) is one of a large group of human cortical malformations that collectively account for a significant percentage of patients with epilepsy, congenital neurological deficits, and...
Am. J. Hum. Genet. - issue: 4 - volume: 70 - pages: 1003-1008.

Lossi, AM.  et al. 2002

Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation

Non-syndromic X linked mental retardation (MRX) is a heterogeneous group of conditions in which all patients have mental retardation as the only constant phenotypic feature. We have identified a...
J. Med. Genet. - issue: 2 - volume: 39 - pages: 113-117.

Moncla, A.  et al. 2002

Polymorphisms in the C-terminal domain of MECP2 in mentally handicapped boys: implications for genetic counselling

Numerous recent reports have proposed that mutations in the C-terminal domain of the MECP2 gene could be a frequent cause of mental retardation in males. We have identified two mutations in this...
Eur. J. Hum. Genet. - issue: 1 - volume: 10 - pages: 86-89.

Villard, L.  et al. 2001

Segregation of a totally skewed pattern of X chromosome inactivation in four familial cases of Rett syndrome without MECP2 mutation: implications for the disease

BACKGROUND: Rett syndrome is a neurodevelopmental disorder affecting only girls; 99.5% of Rett syndrome cases are sporadic, although several familial cases have been reported. Mutations in the MECP2...
J. Med. Genet. - issue: 7 - volume: 38 - pages: 435-442.

Briault, S.  et al. 2000

Mapping of X chromosome inversion breakpoints [inv(X)(q11q28)] associated with FG syndrome: a second FG locus [FGS2]?

FG syndrome is an X-linked condition comprising mental retardation, congenital hypotonia, macrocephaly, distinctive facial changes, and constipation or anal malformations. In a linkage analysis, we...
Am. J. Med. Genet. - issue: 2 - volume: 95 - pages: 178-181.

Villard, L.  et al. 2000

Two affected boys in a Rett syndrome family: clinical and molecular findings

BACKGROUND: The authors report a family in which two boys had severe neonatal encephalopathy of unknown origin. They both presented with the same condition and died of severe apnea before they were 1...
Neurology - issue: 8 - volume: 55 - pages: 1188-1193.

Lossi, AM.  et al. 2000

Exclusion of nine candidate genes for their involvement in X-linked FG syndrome (FGS1) in three families


Am. J. Med. Genet. - issue: 5 - volume: 94 - pages: 386-388.

Laugier-Anfossi, F.  et al. 2000

Molecular characterization of a new human T-box gene (TBX22) located in xq21.1 encoding a protein containing a truncated T-domain

We are conducting a systematic transcriptional mapping of the Xq12-q21 region of the human X chromosome in order to identify new genes potentially involved in X-linked mental retardation phenotypes....
Gene - issue: 2 - volume: 255 - pages: 289-296.

Bienvenu, T.  et al. 2000

MECP2 mutations account for most cases of typical forms of Rett syndrome

Rett syndrome (RTT) is a severe progressive neurological disorder that affects almost exclusively females, with an estimated prevalence of approximately one in 10 000-15 000 female births. Most cases...
Hum. Mol. Genet. - issue: 9 - volume: 9 - pages: 1377-1384.

Villard, L.  et al. 2000

Identification of a mutation in the XNP/ATR-X gene in a family reported as Smith-Fineman-Myers syndrome


Am. J. Med. Genet. - issue: 1 - volume: 91 - pages: 83-85.

Villard, L.  et al. 2000

Linkage of X-linked myopathy with excessive autophagy (XMEA) to Xq28

X-linked myopathy with excessive autophagy (XMEA, MIM 310440) is a rare inherited mild myopathy. We have used 32 polymorphic markers spanning the entire X chromosome to exclude most of the chromosome...
Eur. J. Hum. Genet. - issue: 2 - volume: 8 - pages: 125-129.

Friez, MJ.  et al. 2000

Evidence that a dodecamer duplication in the gene HOPA in Xq13 is not associated with mental retardation

A recent study suggested that a dodecamer duplication in exon 42 of the HOPA gene in Xq13 may be a significant factor in the etiology of X-linked mental retardation. In an effort to investigate this...
Hum. Genet. - issue: 1 - volume: 106 - pages: 36-39.

Lévy, N.  et al. 1999

A polymorphic microsatellite XNP-GT in the XNP/ATRX gene's promotor allows familial indirect diagnosis


Hum. Mutat. - issue: 5 - volume: 14 - pages: 448.

Villard, L.  et al. 1999

Two unrelated patients with inversions of the X chromosome and non-specific mental retardation: physical and transcriptional mapping of their common breakpoint region in Xq13.1

Two unrelated mildly retarded males with inversions of the X chromosome and non-specific mental retardation (MRX) are described. Case 1 has a pericentric inversion 46,Y,inv(X) (p11.1q13.1) and case 2...
J. Med. Genet. - issue: 10 - volume: 36 - pages: 754-758.

Villard, L.  et al. 1999

Characterization of xnp-1, a Caenorhabditis elegans gene similar to the human XNP/ATR-X gene

We report the characterization of a new Caenorhabditis elegans gene, xnp-1, that encodes the closest known non-mammalian relative of the human XNP/ATR-X protein. Mutations in the corresponding gene...
Gene - issue: 1 - volume: 236 - pages: 13-19.

Lossi, AM.  et al. 1999

Mutation of the XNP/ATR-X gene in a family with severe mental retardation, spastic paraplegia and skewed pattern of X inactivation: demonstration that the mutation is involved in the inactivation bias


Am. J. Hum. Genet. - issue: 2 - volume: 65 - pages: 558-562.

Abidi, F.  et al. 1999

Carpenter-Waziri syndrome results from a mutation in XNP


Am. J. Med. Genet. - issue: 3 - volume: 85 - pages: 249-251.

Villard, L.  et al. 1999

Transcript map of the human chromosome Xq11-Xq21 region: localization of 33 novel genes and one pseudogene

The human Xq11-Xq21.3 region has been implicated in several inherited disorders including dystonia-parkinsonism (DYT3), sideroblastic anemia and several specific and non-specific forms of mental...
Gene - issue: 1-2 - volume: 235 - pages: 43-50.

Holden, J. J.  et al. 1999

Eighth International workshop on the fragile X syndrome and X-linked mental retardation, August 16-22, 1997


Am. J. Med. Genet. - issue: 4 - volume: 83 - pages: 221-236.

Villard, L.  et al. 1999

Evaluation of a mutation screening strategy for sporadic cases of ATR-X syndrome

We report on the evaluation of a strategy for screening for XNP/ATR-X mutations in males with mental retardation and associated dysmorphology. Because nearly half of the mutations in this gene...
J. Med. Genet. - issue: 3 - volume: 36 - pages: 183-186.

Tassone, F.  et al. 1999

Structures, sequence characteristics, and synteny relationships of the transcription factor E4TF1, the splicing factor U2AF35 and the cystathionine beta synthetase genes from Fugu rubripes

A cosmid containing the beta-amyloid precursor protein (APP) from Fugu rubripes has been completely sequenced. In addition to APP, the cosmid contains the E4TF1-60 transcription factor, the U2AF35...
Gene - issue: 2 - volume: 226 - pages: 211-223.

Cardoso, C.  et al. 1998

Specific interaction between the XNP/ATR-X gene product and the SET domain of the human EZH2 protein

Mutations in the XNP gene result in different inherited disorders, including the ATR-X syndrome which is characterized by mental retardation (MR) associated with alpha-thalaessemia. Amino acid...
Hum. Mol. Genet. - issue: 4 - volume: 7 - pages: 679-684.

Villard, L.  et al. 1998

Analysis of pufferfish homologues of the AT-rich human APP gene

Mutations in the beta-amyloid precursor protein (APP) gene are associated with some forms of Familial Alzheimer's Disease. The human APP gene is large, the 19 exons span approximately 300 kb, and...
Gene - issue: 1 - volume: 210 - pages: 17-24.

Villard, L.  et al. 1997

Determination of the genomic structure of the XNP/ATRX gene encoding a potential zinc finger helicase

The XNP/ATR-X gene is involved in several X-linked mental retardation phenotypes: the ATR-X syndrome, the Juberg-Marsidi syndrome, and some severe mental retardation phenotypes without...
Genomics - issue: 2 - volume: 43 - pages: 149-155.

Ronce, N.  et al. 1997

A C2055T transition in exon 8 of the ATP7A gene is associated with exon skipping in an occipital horn syndrome family


Am. J. Hum. Genet. - issue: 1 - volume: 61 - pages: 233-238.

Villard, L.  et al. 1997

Map location, genomic organization and expression patterns of the human RED1 RNA editase

A cDNA fragment containing sequences homologous to the rat RED1 RNA editase gene was recently identified on human chromosome 21. Here we report the location of this cDNA in distal 21q22.3 near the...
Somat. Cell Mol. Genet. - issue: 2 - volume: 23 - pages: 135-145.

Raynaud, M.  et al. 1996

X-linked mental retardation with neonatal hypotonia in a French family (MRX15): gene assignment to Xp11.22-Xp21.1

Linkage analysis was performed in a family with non-specific X-linked mental retardation (MRX 15). Hypotonia in infancy was the most remarkable physical manifestation. The severity of mental...
Am. J. Med. Genet. - issue: 1 - volume: 64 - pages: 97-106.

Villard, L.  et al. 1996

A point mutation in the XNP gene, associated with an ATR-X phenotype without alpha-thalassemia

We have previously reported the isolation of a gene from Xq13, coding for a putative regulator of transcription (XNP). It is a member of the helicase family, and has now been shown to be the gene...
Eur. J. Hum. Genet. - issue: 6 - volume: 4 - pages: 316-320.

Villard, L.  et al. 1996

XNP mutation in a large family with Juberg-Marsidi syndrome


Nat. Genet. - issue: 4 - volume: 12 - pages: 359-360.

Villard, L.  et al. 1996

Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia

We have previously reported the isolation of a gene from Xq13 that codes for a putative regulator of transcription (XNP) and has now been shown to be the gene involved in the X-linked...
Am. J. Hum. Genet. - issue: 3 - volume: 58 - pages: 499-505.

Villard, L.  et al. 1995

Use of interspersed repetitive sequences-PCR products for cDNA selection

In order to increase the efficiency of cDNA selection approaches, we describe the use of interspersed repetitive sequences-PCR (IRS-PCR) products to isolate genes from large-insert genomic clones....
Mamm. Genome - issue: 9 - volume: 6 - pages: 617-622.

Gibbons, RJ.  et al. 1995

Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome)

The ATR-X syndrome is an X-linked disorder comprising severe psychomotor retardation, characteristic facial features, genital abnormalities, and alpha-thalassemia. We have shown that ATR-X results...
Cell - issue: 6 - volume: 80 - pages: 837-845.

Villard, L.  et al. 1995

Construction of a YAC contig spanning the Xq13.3 subband

The loci involved in several X-linked mental retardation syndromes have been linked to the pericentromeric region of the X chromosome long arm (Xq12-q21). To isolate candidate genes for these...
Genomics - issue: 1 - volume: 26 - pages: 115-122.

Clark, PA.  et al. 1994

Deletion mapping of the DXS986, DXS995, and DXS1002 loci defines their order within Xq21

The three microsatellite repeat loci, DXS986, DXS995, and DXS1002, have been mapped to Xq13.2-21.1. We report here their relative order and their localisation within Xq21. These loci will be useful...
J. Med. Genet. - issue: 4 - volume: 31 - pages: 344-345.

Gecz, J.  et al. 1994

Cloning and expression of the murine homologue of a putative human X-linked nuclear protein gene closely linked to PGK1 in Xq13.3

Several human inherited diseases have been localized to the Xq13.3 region of the human X chromosome (X-linked dystonia with Parkinsonism, sideroblastic anemia, SCID, Menkes disease and X-linked mental...
Hum. Mol. Genet. - issue: 1 - volume: 3 - pages: 39-44.

Gecz, J.  et al. 1993

Physical and transcriptional mapping of DXS56-PGK1 1 Mb region: identification of three new transcripts

Several new techniques for isolation expressed sequences have been recently described considerably speeding up the identification of unknown genes. Here we present a transcriptional map of the 1 Mb...
Hum. Mol. Genet. - issue: 9 - volume: 2 - pages: 1389-1396.