Département CNS/NET

Message non reçu : lorsque le système nerveux et le système endocrinien communiquent mal

L’essentiel de la communication dans notre organisme est orchestrée par deux systèmes majeurs: le système nerveux et le système endocrinien. Le système nerveux permet de transmettre des messages rapidement le long de neurones depuis le cerveau ou la moelle épinière jusqu’aux différentes parties du corps. Il contrôle tous les mouvements volontaires et involontaires qui assurent le fonctionnement de base de l’organisme. Le système endocrinien, lui, utilise des hormones pour transmettre des message sur le plus long terme qui servent à affiner nombre de fonctions telles que la digestion, la pression artérielle, la croissance, la reproduction ou encore la lactation. Ces deux systèmes de communication s’entremêlent au niveau de l’hypothalamus, une structure à la base du cerveau antérieur qui intègre des messages entrants du système nerveux et contrôle l’hypophyse, la glande mère du système endocrinien. Un grand nombre de maladies génétiques rares affectent les sytèmes nerveux et endocrinien et sont à l’origine respectivement de déficiences intellectuelles (comme le syndrome de Rett et plusieurs encéphalopathies épileptiques précoces) et de déséquilibres hormonaux, qui affectent grand nombre de fonctions de l‘organisme.

Les chercheurs et cliniciens du département CNS/NET contribuent largement à améliorer la compréhension et le diagnostic des maladies rares des systèmes nerveux et neuroendocrinien. Ils ont amplement déchiffré leurs causes génétiques, explorent actuellement les mécanismes responsables de leurs manifestations pathologiques et développent des pistes thérapeutiques qui dores et déjà s’annoncent prometteuses.

Le département CNS/NET rallie un ensemble unique de compétences allant de l’expertise clinique au chevet des patients  à la recherche préclinique, en passant par la maîtrise de la génétique moléculaire, la neurophysiologie et la neuroendocrinologie. Ce rassemblement de forces a déjà permis au département d ‘atteindre d’importantes avancées scientifiques et d’accélérer leur entrée en phase de développement clinique pour le traitement des patients.



Améliorer le diagnostic des déficiences intellectuelles

Les déficiences intellectuelles (DI) se caractérisent par d’importantes limitations du fonctionnement intellectuel et des habiletés adaptatives d’un individu, c’est à dire sa responsabilité sociale et sa capacité à accomplir les tâches du quotidien de manière indépendante.  Ces déficiences concernent près de 3% de la population représentant ainsi un problème majeur de santé publique à travers le monde. Des progrès considérables ont été accomplis en termes de diagnostic au cours des vingt dernières années, mais 50% des patients atteints de DIs restent encore dans l’errance diagnostique. Pour pallier cette défaillance,  l’équipe de Laurent Villard, entre autres, est à la recherche des causes génétiques de ces affections. A ce jour, ils ont déjà identifié plusieurs nouveaux gènes responsables de DIs et ont amplement éclairci la compréhension des mécanismes pahologiques liés à des mutations dans ces gènes.

Une cohorte unique de 980 patients

Les scientifiques s’intéressent tout particulièrement aux encéphalopathies épileptiques précoces (EEP). Pour réussir à mieux les diagnostiquer, ils ont entrepris de former une cohorte unique au monde qui aujourd’hui rassemble 980 patients. Cet effort a déjà porté ses fruits puisqu’il a permis d’identifier plusieurs gènes associés à de EEP, et de confirmer que le gène KCNQ2 est le gène le plus fréquemment muté.

« Des mutations du gène KCNQ2 avaient jusqu’alors été associées au syndrome des convulsions néonatales bénignes familiales (BFNC), une forme rare d’épilepsie qui survient chez le nouveau-né mais dont le pronostic est habituellement bon ; les convulsions disparaissent avec l’âge, les patients ne présentent pas d’anomalies neurologiques, et leur développement neurocognitif est normal », explique Mathieu Milh, le neurologue responsable des aspects cliniques de ce projet dans le laboratoire de Laurent Villard.  « Ce fut une grande surprise que de découvrir que KCNQ2 est un gène important dans les EEP : nous avons identifié en tout 41 mutations différentes du gène dans notre cohorte ».

KCNQ2 code pour une protéine qui participe à la formation de canaux potassiques dans les neurones et qui est donc cruciale pour assurer la communication dans le cerveau. Les chercheurs ont établi des collaborations avec INMED (Inserm U1249) et l'Institut des Neurosciences de La Timone (CNRS) pour tenter de comprendre au niveau cellulaire en quoi ces deux populations de patients sont différentes, et pourquoi alors que certaines mutations provoquent une affection « légère » de type BFNC, d’autres mutations du même gène conduisent à des EEP, qui elles sont beaucoup plus sévères.  Le but ultime de ce projet est de pouvoir proposer aux patients atteints d’EEP des traitements pharmacologiques efficaces qui pour l’instant sont inexistants. Ces projets ont été soutenus par l'ANR, et le sont à nouveau en 2019 avec le projet IMprove qui débutera cet automne (AAPG 2019).

L’initiative est bien plus avancée dans le domaine du syndrome de Rett, une déficience intellectuelle qui occupe les chercheurs dans le laboratoire de Laurent Villard depuis plusieurs années.

Le syndrome de Rett : une maladie neurologique rare

Le Syndrome de Rett (RTT) est une déficience intellectuelle grave décrite pour la première fois par le pédiatre autrichien Andreas Rett. Il se caractérise par un développement cérébral normal jusqu’à l’âge de 6 à 18 mois, âge à partir duquel ce développement commence à régresser pour finalement s’arrêter. Alors qu’une déficience intellectuelle sévère s’installe, le périmètre crânien cesse de progresser normalement, provoquant ainsi une microcéphalie acquise. Les patientes, qui sont dans leur quasi-totalité des filles, perdent progressivement leurs acquis, tels que la marche ou le langage. Elles font également face à des complications supplémentaires, problèmes moteurs, épilepsies, convulsions et troubles respiratoires à l’origine d’épisodes d’hyperventilations et d’apnées.  

En 1999, le laboratoire de Huda Zoghbi (Houston, Texas, États-Unis) découvre le gène responsable pour la plupart des cas de RTT, le gène MECP2, qui se situe au niveau du chromosome X, en position Xq28. Depuis, le laboratoire de Laurent Villard a entrepris une recherche exhaustive de mutations dans ce même gène parmi un ensemble de patients français, et a démontré que des mutations de MECP2 sont également à l’origine d’autres types de DIs, y compris des cas d’encéphalopathies sévères touchant les garçons.

Des mécanisme moléculaire aux traitements pour les patients RTT

Afin de mieux comprendre les mécanismes moléculaires qui déclenchent le syndrome de Rett, Laurent Villard et ses collaborateurs s’intéressent depuis des années à un modèle murin de la maladie développé dans le laboratoire d’Adrian Bird (Edinburgh, Royaume-Uni). Leurs découvertes constitutent des avancées majeures dans le domaine qui ont permis de développer de potentielles voies thérapeutiques prometteuses pour le traitement des patients RTT.

Les chercheurs ont remarqué que les souris Mecp2 présentaient des troubles respiratoires similaires à ceux des patients RTT. Ils ont noté que ces troubles étaient liés à une diminution des niveaux d’un neuromédiateur appelé norépinéphrine (NE) au niveau de la medulla, l’aire du cerveau qui contient les centres respiratoires. À l’époque, cette découverte fut la première description in vivo d’un défaut cellulaire lié à l’absence de Mecp2. De plus, leurs premières recherches suggéraient que les troubles respiratoires pouvaient être corrigés par ajout de NE exogène. L’équipe a donc tenté de provoquer une augmentation des niveaux de NE chez les animaux, en traitant les souris à la désipramine, un composant chimique normalement utilisée pour traiter des patients dépressifs.

« Nous avons administré une dose quotidienne de désipramine aux souris, et avons remarqué non seulement une amélioration des troubles respiratoires, mais également de leur espérance de vie », rapporte Jean-Christophe Roux, en charge du projet Rett dans le laboratoire de Laurent Villard. « À partir de ces résultats très positifs, nous avons initié un essai clinique en collaboration avec le Professeur Josette Mancini de l’Hôpital La Timone à Marseille, pour étudier les effets d’un traitement à la désipramine sur des enfants atteints de Rett ». Les résultats de cet essai clinique de phase II ont été publiés en 2018.

Plus récemment, les chercheurs ont identifié dans les neurones des souris Mecp2 des défauts de transport du BDNF, un facteur crucial pour la croissance et la survie neuronales, ainsi que pour l’établissement de connexions entre neurones. Ils ont démontré qu’une augmentation de la sécrétion de BDNF, en utilisant un composé chimique appelé cysteamine, induit une amélioration significative des défauts moteurs chez les souris RTT et une augmentation de leur espérance de vie. Cette importante découverte est maintenant entrée dans la clinique où un deuxième essai de phase II est en cours pour déterminer l’efficacité d’une traitement à la cystéamine chez des patients Rett.

Ces investigations cherchant à comprendre les dysfonctionnement moléculaires dans le Syndrome de Rett ce sont avérés fructueuses. En effet, en plus de des deux essais décrits ci-dessus, l’équipe de Laurent Villard explore de nouvelles pistes qui semblent prometteuses et offrent des perspectives solides en termes de développement de traitements thérapeutiques.  

Les maladies neuroendocriniennes sont dues à une hyper- ou à une hyposécrétion d’hormones par les glandes endocriniennes. Alors que les maladies liées à une hypersécrétion sont pour la plupart dues à des tumeurs bénignes non-cancéreuses, les maladies liées à une hyposécrétion, appelées déficits hormonaux, peuvent avoir des origines bien différentes. Ces troubles peuvent toucher n’importe quelle glande endocrinienne, mais ceux qui affectent l’hypophyse, la glande mère du système endocrinien, présentent un éventail de conséquences bien plus large sur différentes fonctions biologiques. Dans l’idée de proposer de nouveaux traitements thérapeutiques, le laboratoire de Thierry Brue explore les causes génétiques et les mécanismes moléculaires qui sont à la base des troubles neuroendocriniens. Les chercheurs s’intéressent tout particulièrement au déficit hypophysaire combiné multiple (CPHD : Combined Pituitary Hormone deficiency), pour lequel ils ont dores et déjà identifié un grand nombre de gènes  et de mutations responsables, en partie grâce à la constitution d’une collection internationale d’échantillons ADN provenant de 1200 patients (GENHYPOPIT).

Troubles neuroendocriniens : la clé est dans la balance

«  L’analyse détaillée des échantillons ADN du réseau GENHYPOPIT nous a permis de découvrir un nouveau syndrome qui combine un déficit hormonal à un déficit immunitaire commun variable caractérisé par un défaut dans la production d’anticorps » déclare Thierry Brue. « Nous avons baptisé ce syndrome DAVID, pour ‘Deficit in Anterior pituitary function and Variable Immune Deficiency’ ». Le gène responsable du syndrome de DAVID s’appelle NFKB2 et code pour une sous-unité du complexe NFkB, un facteur de transcription important qui active l’expression d’un nombre de gènes dans les réponses inflammatoires et immunitaires.

En parallèle, le laboratoire s’intéresse également à l’étude des tumeurs neuroendocriniennes (TNE) pour comprendre les signaux qui y entraînent une augmentation de la sécrétion d’hormones. L’équipe a jusqu’à présent identifié plusieurs facteurs impliqués aussi bien dans le CPHD que dans les TNE, mais sur lesquels ils ont des effets opposés. C ‘est le cas du récepteur de l’hormone de croissance (GHR), du récepteur ghréline (GHS-R) , ou encore de Pit-1, un facteur de transcription important pour le développement hypophysaire et  l’expression d’hormones.

Les deux faces de Pit-1

Le gène PIT-1 avait historiquement été impliqué aussi bien à des cas de nanisme que dans des cas de gigantisme. Ce gène code pour un facteur de transcription clé dans la différentiation des cellules endocriniennes et régule l’expression d’hormones telles que l’hormone de croissance ou la prolactine (impliquées respectivement dans la croissance et la lactation).  En 2006, alors que des mutations dans le gène avaient déjà été associées à des cas de CPHD, Thierry Brue, Anne Barlier et leurs collaborateurs démontrent l’implication de PIT-1 cette fois-ci dans les TNE dans lesquelles il agit en facteur de croissance. L’équipe décide alors d’exploiter ces deux faces du rôle de PIT-1 dans le déficits hormonaux et les TNE, et développe une approche de thérapie génique utilisant une version muté de PIT-1 identifiée chez des patients CPHD, Pit-1-R271W, pour traiter l’hypersécrétion et la croissance tumorale dans le syndrome opposé, les tumeurs neuroendocriniennes.

«  Nos résultats montrent que le mutant Pit1-R271W bloque l’hypersécrétion hormonale de cellules issues de TNE et induit la mort cellulaire aussi bien in vitro que in vivo chez la souris » décrit Anne Barlier, en charge de ce projet dans le laboratoire de Thierry Brue. « Cette stratégie pourrait s’avérer prometteuse pour le traitement de tumeurs de l‘hypophyse par thérapie génique »

En plus de poursuivre la recherche de mutations génétiques liées à des maladies neuroendocriniennes, les chercheurs mobilisent actuellement leurs efforts pour établir de nouveaux modèles cellulaire qui permettraient de mieux comprendre ces troubles, ainsi que pour développer de nouvelles stratégies thérapeutiques.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Am J Hum Genet. 2019"", .  et al. 0

PubMed""

; Analysis of the Phenotypes in the Rett Networked Database.
Armstrong J - issue: Pineda M - volume: Bahi-Buisson N - pages: Clarke A.

Am J Hum Genet. 2019"", .  et al. 0

PubMed""

; Analysis of the Phenotypes in the Rett Networked Database.
Armstrong J - issue: Pineda M - volume: Bahi-Buisson N - pages: Clarke A.