Depuis de nombreuses années, notre travail est focalisé sur les maladies neurologiques d'origine génétique qui empêchent le développement normal du cerveau des enfants. Plus spécifiquement, nous étudions les encéphalopathies épileptiques (DEE), le syndrome de Rett et les formes syndromiques de déficience intellectuelle.

Nous avons trois objectifs principaux :

  1. Contribuer à l'accroissement des connaissances dans le domaine des maladies neurologiques pédiatriques ;
  2. Améliorer le diagnostic et le conseil génétique pour ces maladies ;
  3. Proposer de nouvelles approches thérapeutiques.

Notre équipe est composée de 4 chercheurs permanents (Inserm et CNRS), 2 médecins 2 ingénieurs et un nombre variable de post-doctorants et étudiants. Nous avons des compétences complémentaires dans le domaine de la génétique clinique, de la génétique moléculaire, de la neurophysiologie, de l'électrophysiologie et de l'étude du comportement animal.

N'hésitez pas à nous contacter à cette adresse <laurent.villard@univ-amu.fr> si vous voulez nous rejoindre.

Nos travaux sont présentés en détails ci-dessous.



Projets

L’épilepsie est une affection neurologique fréquente (environ 1%) et très hétérogène. Parmi les différentes formes d’épilepsie de l’enfant, l'équipe s'intéresse à un groupe d’épilepsies génétiques rares : les encéphalopathies épileptiques et développementales (DEE). Ces pathologies sont caractérisées par : 1- leur survenue précoce, dès les premières semaines de vie ; 2- des manifestations cliniques à type de myoclonies erratiques, des spasmes et/ou de crises partielles quasi-continues ; 3- un EEG interictal très anormal ; 4- une évolution très sévère avec une mortalité importante pendant les premières années de vie ; 5- une absence de traitement efficace, en particulier des anti-épileptiques conventionnels. L'immense majorité des cas étant sporadique, le seul moyen d'intervenir efficacement sera de mettre au point de nouvelles approches thérapeutiques. C'est notre objectif affiché.

 

> Activité de diagnostic hospitalier

 

Depuis plus de 10 ans, Laurent Villard supervise le diagnostic moléculaire des épilepsies d'origine génétique au sein de l'Assistance Publique Hôpitaux de Marseille. Il dispose pour cela d'un agrément de l’Agence de Biomédecine. Cette activité permet de poser un diagnostic dans 40% des cas quand les crises sont présentes dès la première semaine de vie, permet de renforcer la connaissance clinique et moléculaire de la pathologie, et de renforcer l'expertise de l'équipe en la matière ; elle permet d'augmenter la taille des cohortes déjà constituées et de développer des projets de recherche à visée translationnelle (cf. infra). Avec nos collègues des CHU de Lyon, La Pitié Salpétrière et Strasbourg nous avons créé en 2015 un réseau national de diagnostic des épilepsies génétiques (réseau ANPGM EPIGENE ; voir PMID 35091117). La cohorte hospitalière a désormais dépassé les 2500 patients.

 

> Identification de nouveaux gènes

 

En collaboration avec l'équipe de Kerstin Kutsche à Hambourg, nous avons identifié deux nouveaux gènes d'épilepsie néonatale (PMID 20890276). Il s'agit de deux sous-unités du récepteur NMDA codées par les gènes GRIN2B et GRIN2A. En collaboration avec d'autres équipes, nous avons également démontré que les mutations hétérozygotes composites dans le gène TBCD124 sont fréquentes et provoquent plusieurs types d'épilepsie (PMID 23526554; PMID 25769375; PMID 26207815).

Nous avons participé à l'identification d'un nouveau gène d'encéphalopathie épileptique avec l'équipe de génétique du CHU de Dijon (PMID 24995870). Plus récemment, nous avons identifié plusieurs gènes grâce au séquençage d'exome : UBR5 étudié avec Philippe Campeau au Canada (article en préparation), PCDHGC4 (PMID 34244665), KMT2E (PMID 31079897) ou SYT1 actuellement étudié en collaboration avec l'équipe de James Rothman à Yale (USA). Nous avons également participé à la mise en point d’un système prédictif pour les gènes de pathologies liés au chromosome X (PMID 36323681).

Notre équipe a obtenu un financement H2020 dans le cadre de l'appel Twinning 2019. Ce programme nous a jumelé avec la Tunisie afin de mieux appréhender le paysage moléculaire des épilepsies récessives (Service de Neurologie Pédiatrique, Hôpital Hedi Chaker de Sfax). Des études génétiques utilisant le NGS seront désormais effectuées à Sfax (PMID 34273994) puis éventuellement partagées avec notre équipe pour l'analyse des variants et leur étude fonctionnelle.

 

> Physiopathologie des DEE

 

Le gène KCNQ2 est le gène majeur des DEE néonatales. Ce gène code pour une sous-unité d'un canal potassique produisant le courant M, responsable de la phase d'hyperpolarisation consécutive à un potentiel d'action. A travers l'activité de diagnostic de l'équipe, nous avons identifié plusieurs dizaines de variants pathogènes de novo dans ce gène. Historiquement, les variants pathogènes de KCNQ2 étaient connus chez des patients ayant une épilepsie néonatale familiale bénigne (BFNS). Chez les patients BFNS, le pronostic neurologique est bon et le développement est globalement normal. Les formes sont volontiers familiales. Le fait que des variants pathogènes dans le même gène provoquent des tableaux cliniques si différents (et si sévères) nous a conduit à émettre l'hypothèse que le canal potassium contenant KCNQ2 pourrait être différemment affecté dans les deux populations de patients. Nous avons donc construit un programme de recherche sur la physiopathologie des DEE liées aux mutations de KCNQ2 en collaboration avec l'INMED (Inserm U1249), l'INT (CNRS UMR7289) et i-Stem (Centre d'Etude des Cellules Souches, Evry) (financement ANR 2014 et ANR 2019, L. Villard coordinateur).

 

Afin de disposer de modèles cellulaires adaptés à nos projets, nous avons produit des lignées de cellules pluripotentes induites (iPS). Grâce à sa collaboration avec i-Stem, notre équipe a appris à produire des neurones corticaux humains matures. Nous avons également produit le premier modèle de DEE liée au gène KCNQ2 sous la forme d’une souris knock-in qui contient un variant récurrent associé à un phénotype sévère et typique (pour revue sur les modèles voir PMID 36047730). Nos travaux récents montrent que ce modèle reproduit parfaitement la pathologie attendue (PMID 32239694). Ce modèle a suscité l'intérêt de plusieurs compagnies pharmaceutiques et nous avons entamé des essais pharmacologiques pour certaines molécules candidates issues de ces compagnies (NDA et licences non exclusives signés).

 

Nos recherches sur les DEE liées à KCNQ2 ont d’ores et déjà abouti à des résultats originaux concernant les mécanismes de l'épilepsie. Nous avons démontré que certaines mutations sont capables d'induire une délocalisation des canaux KCNQ2, ce qui constitue un nouveau mécanisme pour cette pathologie (PMID 26007637). Un autre travail a montré que certaines mutations gain de fonction avaient un effet similaire aux mutations perte de fonction (PMID 27030113). Plus récemment, nous avons montré le rôle de Kcnq2 dans la genèse des rythmes moteurs et caractérisé l'activité corticale chez les souris knock-in de l'équipe (PMID 33186352; PMID 35389519). Nous avons également mis au point un système de déclenchement des crises à volonté dans ce modèle et caractérisé les régions cérébrales activées par les crises (PMID 37187037).

 

> Projets

 

Le consortium financé par l'European Joint Program on Rare Diseases 2020 (France, Belgique, Allemagne, Italie – projet TreatKCNQ) auquel nous appartenons a pour objectif de mettre au point et de tester des dérivés plus sûrs et plus efficaces de la retigabine, une molécule active sur les canaux potassiques KCNQ mais qui a été retirée du marché à cause d'effets secondaires inattendus. Le projet vise également à identifier de nouveaux activateurs et bloqueurs des canaux KCNQ qui seront testés dans nos modèles (neurones humains et souris knock-in). Nous avons désormais identifié plusieurs molécules candidates que mon équipe va tester. Nous étudierons aussi le potentiel des oligonucléotides antisens pour réaliser des inactivations allèle-spécifique.

En parallèle, nous avons poursuivi l'étude du segment initial de l'axone (AIS) dans les modèles neuronaux humains et dans la souris knock-in afin de déterminer si des mécanismes de compensation liés à la structure de l'AIS se mettent en place dans les DEE liées à KCNQ2. Nous avons débuté des études "omiques" (RNA-seq et protéomique) dont les résultats vont être complétés et intégrés dans les mois qui viennent (avec l'aide de l'équipe de biologie des systèmes de notre unité, Anaïs Baudot). Nous avons prévu d'étudier les modifications neurochimiques dans le cerveau de nos animaux modèles. Nous disposons d'un système d'enregistrement sur microélectrode arrays qui va nous servir à étudier la signature électrophysiologique des neurones humains issus de patients.

Axe 2 : Déficiences Intellectuelles : des causes à la physiopathologie

Les troubles du neurodéveloppement (TND) sont des affections fréquentes qui touchent environ 1 français sur 10. Parmi ces pathologies, on trouve les troubles du développement intellectuel (TDI) qui se définissent par « un déficit général des capacités intellectuelles accompagné par une altération du fonctionnement adaptatif » Ces affections sont un motif fréquent de consultation médicale, puisqu’elles concernent près de 3 % de la population générale. Les TDI sont des troubles extrêmement hétérogènes, cliniquement et génétiquement, et leurs origines sont très diverses. Malgré les progrès en cytogénétique et en biologie moléculaire de ces dernières années, l’origine de près de 50% des TDI reste encore indéterminée. L’identification de la cause de ces maladies est essentielle pour poser un diagnostic et proposer une prise en charge adaptée des patients. D’un point de vue plus fondamental, l’identification des causes des TDI nous permettra de mieux comprendre le développement du cerveau et la mise en place des fonctions cognitives.

  • Identification de nouveaux gènes

De par notre étroite collaboration avec les services de génétique clinique et de neurologie pédiatrique, nous avons commencé la création d’une cohorte de plus d’une vingtaine de patients présentant des TND. Grâce à la technique du séquençage de l’exome, nous avons ainsi pu décrire deux nouveaux syndromes en identifiant des variants dans les gènes PCDHGC4 (PMID : 34244665), responsable d’un nouveau syndrome neurodéveloppemental associant DI, microcéphalie, épilepsie et atteintes articulaires, et NAPB (PMID : 37014259) qui entraîne une encéphalopathie épileptique et développemental (DEE) spécifique. Nous avons également identifié des variants dans des gènes connus tels que TRAPPC2L (PMID : 36849228), DYNC1H1, SNX14 ou NDST1 (article en révision).

Cependant, malgré la puissance de l’exome, environ 25 % des patients de notre cohorte sont encore sans diagnostic. Pour ces derniers, nous voulons améliorer les outils bio-informatiques pour mieux identifier des CNV (Copy Number Variation) ou des éléments transposables qui pourraient expliquer la pathologie. Dans ce but, nous participons à une étude pilote menée par le Dr. S. Gorokhova, en collaboration avec la plateforme de génomique et de bio-informatique (GBiM, Genomic Bioinformatic Marseille) hébergée par le MMG, qui a obtenu le soutien financier de la Fondation Maladies Rares.

En parallèle, nous voulons également combiner l’analyse du transcriptome aux données de séquençage, que ce soit l’exome ou le génome. Le transcriptome, obtenu par le séquençage de l’ARN (RNASeq), permet de quantifier l’expression des transcrits et d’identifier des transcrits alternatifs. Nous voudrions analyser le transcriptome issu du sang ou des fibroblastes des patients, soit de neurones dérivés d’iPSC (cellules souches pluripotentes induites) pour ne manquer aucun gène qui serait spécifiquement exprimé dans les neurones.

 

  • Analyse fonctionnelle du gène NDST1

Lorsque des variants sont identifiés dans un gène, il est essentiel de réaliser une étude fonctionnelle approfondie afin de confirmer leur implication dans la pathologie observée chez les patients. Récemment, nous avons mis en évidence le même variant homozygote, chez deux familles indépendantes, dans un gène connu pour être responsable de TDI : le gène NDST1 ((N-déacétylase/N-sulfotransférase member 1). Ce gène code pour une enzyme bi-fonctionnelle indispensable à la formation de l’héparane sulfate. Cependant, aucune analyse fonctionnelle des différents variants identifiés n’avait été faite. Afin de discriminer entre un polymorphisme rare, qui n’expliquerait pas la maladie, et un variant pathogène, nous avons établi une collaboration avec le Dr. Lena Kjellén (Université d’Uppsala, Suède) pour évaluer les activités enzymatiques de la protéine mutante (article en révision).

Afin de compléter ces résultats, nous aimerions poursuivre l’étude des différents variants identifiés pour confirmer que les deux domaines de cette enzyme sont bien impliqués dans la pathologie.

  • Implication de l’autophagie dans la déficience intellectuelle

L’autophagie est un mécanisme d’autodigestion des composants intracellulaires qui joue un rôle physiologique essentiel dans la croissance cellulaire, la différenciation et surtout le maintien de l’homéostasie en éliminant et en remplaçant continuellement les protéines et organites non fonctionnels. Cette voie est d’autant plus importante dans les neurones puisque ce sont des cellules post-mitotiques. Récemment, nous avons mis en évidence un variant, chez deux frères présentant un TDI syndromique, dans un gène impliqué dans la voie de l’autophagie : le gène RMC1 (Regulator of Mon1-Ccz1). Ce gène code une protéine qui régule l’activité du complexe Mon1-Ccz1 qui est nécessaire au recrutement de Rab7 et à la maturation de l’autophagosome. Comme ce gène n’est relié à aucune maladie connue et qu’aucune autre famille n’a encore été identifiée, la validation fonctionnelle de ce variant est indispensable.

Nos premiers résultats sont encourageants puisqu’ils montrent que la voie de l’autophagie semble être perturbée dans les fibroblastes des patients. La suite de notre projet consistera à confirmer ses résultats et à analyser plus en profondeur la voie de l’autophagie dans les fibroblastes. Nous voulons également développer des neurones dérivés d’iPSC pour étudier cette voie dans ces cellules où l’autophagie joue un rôle primordial dans l’homéostasie des protéines et des organites, et permet la croissance axonale et le développement des épines dendritiques. Nous pourrons également étudier leurs propriétés électrophysiologiques à l’aide d’un système MEA (multi-electrode array) qui nous permettra d’analyser la communication au sein du réseau neuronal.

Brun, L.  et al. 2023

Ultrasound-induced seizures in a mouse model of KCNQ2-NEO-DEE.

PURPOSE: KCNQ2 neonatal developmental and epileptic encephalopathy (NEO-DEE) is characterized by intractable seizures accompanied by an abnormal neurodevelopment. In a mouse model of NEO-DEE carrying...
Epilepsy Res - issue: - volume: 193 - pages: 107160.

Engel, C.  et al. 2023

BRAT1-related disorders: phenotypic spectrum and phenotype-genotype correlations from 97 patients.

BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures...
Eur J Hum Genet - issue: - volume: - pages: .

Mignon-Ravix, C.  et al. 2023

NAPB and developmental and epileptic encephalopathy: Description of the electroclinical profile associated with a novel pathogenic variant.

Developmental and epileptic encephalopathies (DEE) are a group of neurodevelopmental disorders characterized by epileptic seizures associated with developmental delay or regression. DEE are...
Epilepsia - issue: 6 - volume: 64 - pages: e127-e134.

Abaji, M.  et al. 2023

TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype.

The TRAPP (TRAfficking Protein Particle) complexes are evolutionarily conserved tethering factors involved in the intracellular transport of vesicles for secretion and autophagy processes. Pathogenic...
J Med Genet - issue: - volume: - pages: jmedgenet-2022-108677.

Brock, S.  et al. 2023

Overlapping cortical malformations in patients with pathogenic variants in GRIN1 and GRIN2B.

BACKGROUND: Malformations of cortical development (MCDs) have been reported in a subset of patients with pathogenic heterozygous variants in GRIN1 or GRIN2B, genes which encode for subunits of the...
J Med Genet - issue: 2 - volume: 60 - pages: 183-192.

Parenti, I.  et al. 2022

The different clinical facets of SYN1-related neurodevelopmental disorders.

Synapsin-I (SYN1) is a presynaptic phosphoprotein crucial for synaptogenesis and synaptic plasticity. Pathogenic SYN1 variants are associated with variable X-linked neurodevelopmental disorders...
Front Cell Dev Biol - issue: - volume: 10 - pages: 1019715.

Leitão, E.  et al. 2022

Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X.

Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of...
Nat Commun - issue: 1 - volume: 13 - pages: 6570.

Brun, L.  et al. 2022

Mouse models of Kcnq2 dysfunction.

Variants in the Kv7.2 channel subunit encoded by the KCNQ2 gene cause epileptic disorders ranging from a benign form with self-limited epileptic seizures and normal development to severe forms with...
Epilepsia - issue: 11 - volume: 63 - pages: 2813-2826.

Maillard, P.  et al. 2022

Molecular and clinical descriptions of patients with GABA(A) receptor gene variants (GABRA1, GABRB2, GABRB3, GABRG2): A cohort study, review of literature, and genotype-phenotype correlation.

OBJECTIVE: γ-Aminobutyric acid (GABA)(A) -receptor subunit variants have recently been associated with neurodevelopmental disorders and/or epilepsy. The phenotype linked with each gene is becoming...
Epilepsia - issue: 10 - volume: 63 - pages: 2519-2533.

Aubert Mucca, M.  et al. 2022

Patients with KCNH1-related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome.

De novo missense variants in KCNH1 encoding Kv10.1 are responsible for two clinically recognisable phenotypes: Temple-Baraitser syndrome (TBS) and Zimmermann-Laband syndrome (ZLS). The clinical...
J Med Genet - issue: 5 - volume: 59 - pages: 505-510.

Biba-Maazou, N.  et al. 2022

Time-limited alterations in cortical activity of a knock-in mouse model of KCNQ2-related developmental and epileptic encephalopathy.

De novo missense variants in the KCNQ2 gene encoding the Kv7.2 subunit of voltage-gated potassium Kv7/M channels are the main cause of developmental and epileptic encephalopathy with neonatal onset....
J Physiol - issue: 10 - volume: 600 - pages: 2429-2460.

Arnaud, L.  et al. 2022

The EPIGENE network: A French initiative to harmonize and improve the nationwide diagnosis of monogenic epilepsies.

BACKGROUND: The EPIGENE network was created in 2014 by four multidisciplinary teams composed of geneticists, pediatric neurologists and neurologists specialized in epileptology and neurophysiology....
Eur J Med Genet - issue: 3 - volume: 65 - pages: 104445.

Borloz, E.  et al. 2021

Rett syndrome: think outside the (skull) box.

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities....
Fac Rev - issue: - volume: 10 - pages: 59.

Iqbal, M.  et al. 2021

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies.

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We...
Genet Med - issue: 11 - volume: 23 - pages: 2138-2149.

Whalen, S.  et al. 2021

Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants.

The BCAP31 gene, located at Xq28, encodes BAP31, which plays a role in ER-to-Golgi anterograde transport. To date, BCAP31 pathogenic variants have been reported in 12 male cases from seven families...
Eur J Hum Genet - issue: 9 - volume: 29 - pages: 1405-1417.

Felix, M.  et al. 2021

Ultrasound-Mediated Blood-Brain Barrier Opening Improves Whole Brain Gene Delivery in Mice.

Gene therapy represents a powerful therapeutic tool to treat diseased tissues and provide a durable and effective correction. The central nervous system (CNS) is the target of many gene therapy...
Pharmaceutics - issue: 8 - volume: 13 - pages: .

Jdila, MB.  et al. 2021

A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity

BACKGROUND: Developmental and epileptic encephalopathies (DEE) are chronic neurological conditions where epileptic activity contributes to the progressive disruption of brain function, frequently...
Orphanet J Rare Dis - issue: 1 - volume: 16 - pages: 317.

Jdila, MB.  et al. 2021

A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) are chronic neurological conditions where epileptic activity contributes to the progressive disruption of brain function, frequently...
Orphanet J Rare Dis - issue: 1 - volume: 16 - pages: 317.

Srivastava, S.  et al. 2021

Expansion of the Genotypic and Phenotypic Spectrum of WASF1-Related Neurodevelopmental Disorder

In humans, de novo truncating variants in WASF1 (Wiskott-Aldrich syndrome protein family member 1) have been linked to presentations of moderate-to-profound intellectual disability (ID), autistic...
Brain Sci - issue: 7 - volume: 11 - pages: 931.

Iqbal, M.  et al. 2021

Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We...
Genet Med - issue: - volume: - pages: .

Le Roux, M.  et al. 2021

CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients.

CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is...
Eur J Paediatr Neurol - issue: - volume: 33 - pages: 75-85.

Le Roux, M.  et al. 2021

CACNA1A-associated epilepsy: Electroclinical findings and treatment response on seizures in 18 patients

CACNA1A pathogenic mutations are involved in various neurological phenotypes including episodic ataxia (EA2), spinocerebellar ataxia (SCA6), and familial hemiplegic migraine (FHM1). Epilepsy is poorly...
Eur J Paediatr Neurol - issue: - volume: 33 - pages: 75-85.

Ehinger, Y.  et al. 2021

Analysis of Astroglial Secretomic Profile in the Mecp2-Deficient Male Mouse Model of Rett Syndrome

Mutations in the X-linked MECP2 gene are responsible for Rett syndrome (RTT), a severe neurological disorder. MECP2 is a transcriptional modulator that finely regulates the expression of many genes,...
Int J Mol Sci - issue: 9 - volume: 22 - pages: 4316.

Aubert Mucca, M.  et al. 2021

Patients with KCNH1-related intellectual disability without distinctive features of Zimmermann-Laband/Temple-Baraitser syndrome

De novo missense variants in KCNH1 encoding Kv10.1 are responsible for two clinically recognisable phenotypes: Temple-Baraitser syndrome (TBS) and Zimmermann-Laband syndrome (ZLS). The clinical...
J Med Genet - issue: - volume: - pages: jmedgenet-2020-107511.

Lo Barco, T.  et al. 2021

SYNGAP1-DEE: A visual sensitive epilepsy.

OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS: Participants with pathogenic SYNGAP1 variants and available...
Clin Neurophysiol - issue: 4 - volume: 132 - pages: 841-850.

Lo Barco, T.  et al. 2021

SYNGAP1-DEE: A visual sensitive epilepsy

OBJECTIVE: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants. METHODS: Participants with pathogenic SYNGAP1 variants and available...
Clin Neurophysiol - issue: 4 - volume: 132 - pages: 841-850.

Whalen, S.  et al. 2021

Further delineation of BCAP31-linked intellectual disability: description of 17 new families with LoF and missense variants

The BCAP31 gene, located at Xq28, encodes BAP31, which plays a role in ER-to-Golgi anterograde transport. To date, BCAP31 pathogenic variants have been reported in 12 male cases from seven families...
Eur J Hum Genet - issue: - volume: - pages: .

Matagne, V.  et al. 2021

Severe offtarget effects following intravenous delivery of AAV9-MECP2 in a female 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 genetic...
Neurobiol Dis - issue: - volume: 149 - pages: 105235.

André, M.  et al. 2021

The phenotype caused by recessive variations in SLC25A22: Report of a new case and literature review.

We describe the clinical, electroencephalography (EEG), and developmental features of a patient with developmental and epileptic encephalopathy due to a homozygous pathogenic variation of...
Arch Pediatr - issue: 1 - volume: 28 - pages: 87-92.

André, M.  et al. 2021

The phenotype caused by recessive variations in SLC25A22: Report of a new case and literature review

We describe the clinical, electroencephalography (EEG), and developmental features of a patient with developmental and epileptic encephalopathy due to a homozygous pathogenic variation of...
Arch Pediatr - issue: 1 - volume: 28 - pages: 87-92.

Borloz, E.  et al. 2021

Rett syndrome: think outside the (skull) box

Rett syndrome (RTT) is a severe X-linked neurodevelopmental disorder characterized by neurodevelopmental regression between 6 and 18 months of life and associated with multi-system comorbidities....
- issue: - volume: - pages: .

El Waly, B.  et al. 2020

Molecular characterization of a 1p36 chromosomal duplication and in utero interference define ENO1 as a candidate gene for polymicrogyria

While chromosome 1p36 deletion syndrome is one of the most common terminal subtelomeric microdeletion syndrome, 1p36 microduplications are rare events. Polymicrogyria (PMG) is a brain malformation...
Eur J Hum Genet - issue: 12 - volume: 28 - pages: 1703-1713.

Verneuil, J.  et al. 2020

The M-current works in tandem with the persistent sodium current to set the speed of locomotion

The central pattern generator (CPG) for locomotion is a set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current (INaP). How they proceed to regulate the...
PLoS Biol - issue: 11 - volume: 18 - pages: e3000738.

Cabasson, S.  et al. 2020

Early-onset epileptic encephalopathy related to germline PIGA mutations: A series of 5 cases

The molecular diagnosis of early-onset epileptic encephalopathy (EOEE), an expanding field in child neurology, is becoming increasingly possible thanks to the widespread availability of...
Eur J Paediatr Neurol - issue: - volume: 28 - pages: 214-220.

Trivisano, M.  et al. 2020

Defining the phenotype of FHF1 developmental and epileptic encephalopathy

Fibroblast growth-factor homologous factor (FHF1) gene variants have recently been associated with developmental and epileptic encephalopathy (DEE). FHF1 encodes a cytosolic protein that modulates...
Epilepsia - issue: 7 - volume: 61 - pages: e71-e78.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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: .

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.