| Title: |
Further characterisation of ARX -related disorders in females due to inherited or de novo variants |
| Authors: |
Gras, Mathilde; Heide, Solveig; Keren, Boris; Valence, Stéphanie; Garel, Catherine; Whalen, Sandra; Jansen, Anna; Keymolen, Kathelijn; Stouffs, Katrien; Jennesson, Mélanie; Poirsier, Céline; Lesca, Gaetan; Depienne, Christel; Nava, Caroline; Rastetter, Agnès; Curie, Aurore; Cuisset, Laurence; Des Portes, Vincent; Milh, Mathieu; Charles, Perrine; Mignot, Cyril; Héron, Delphine |
| Contributors: |
CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC); Université Pierre et Marie Curie - Paris 6 (UPMC); Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM); Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); CHU Trousseau APHP; Vrije Universiteit Brussel Bruxelles (VUB); Hôpital universitaire Robert Debré Reims (CHU Reims); Hospices Civils de Lyon (HCL); University Hospital Essen (AöR); Institut du Cerveau = Paris Brain Institute (ICM); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS); Hôpital Femme Mère Enfant CHU - HCL (HFME); Evaluating, understanding, supporting motor, perceptive and social Trajectories (CRNL-TRAJECTOIRES); Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Hôpital Cochin AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Service de pédiatrie et neurologie pédiatrique; Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Timone CHU - APHM (TIMONE) |
| Source: |
ISSN: 0022-2593. |
| Publisher Information: |
CCSD; BMJ Publishing Group |
| Publication Year: |
2024 |
| Collection: |
HAL Lyon 1 (University Claude Bernard Lyon 1) |
| Subject Terms: |
Epilepsy; Genetic Counseling; Human Genetics; Heredity; and Neonatal Diseases and Abnormalities; Hereditary; Congenital; MESH: Male; MESH: Humans; MESH: Phenotype; MESH: Agenesis of Corpus Callosum; MESH: Female; MESH: Genes; Homeobox; MESH: Homeodomain Proteins; MESH: Autism Spectrum Disorder; MESH: Mutation; MESH: Transcription Factors; MESH: Intellectual Disability; [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics; [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology; [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] |
| Description: |
International audience ; The Aristaless-related homeobox ( ARX ) gene is located on the X chromosome and encodes a transcription factor that is essential for brain development. While the clinical spectrum of ARX -related disorders is well described in males, from X linked lissencephaly with abnormal genitalia syndrome to syndromic and non-syndromic intellectual disability (ID), its phenotypic delineation in females is incomplete. Carrier females in ARX families are usually asymptomatic, but ID has been reported in some of them, as well as in others with de novo variants. In this study, we collected the clinical and molecular data of 10 unpublished female patients with de novo ARX pathogenic variants and reviewed the data of 63 females from the literature with either de novo variants (n=10), inherited variants (n=33) or variants of unknown inheritance (n=20). Altogether, the clinical spectrum of females with heterozygous pathogenic ARX variants is broad: 42.5% are asymptomatic, 16.4% have isolated agenesis of the corpus callosum (ACC) or mild symptoms (learning disabilities, autism spectrum disorder, drug-responsive epilepsy) without ID, whereas 41% present with a severe phenotype (ie, ID or developmental and epileptic encephalopathy (DEE)). The ID/DEE phenotype was significantly more prevalent in females carrying de novo variants (75%, n=15/20) versus in those carrying inherited variants (27.3%, n=9/33). ACC was observed in 66.7% (n=24/36) of females who underwent a brain MRI. By refining the clinical spectrum of females carrying ARX pathogenic variants, we show that ID is a frequent sign in females with this X linked condition. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/37879892; PUBMED: 37879892 |
| DOI: |
10.1136/jmg-2023-109203 |
| Availability: |
https://cnrs.hal.science/hal-04920096; https://cnrs.hal.science/hal-04920096v1/document; https://cnrs.hal.science/hal-04920096v1/file/ARX103.full2025.pdf; https://doi.org/10.1136/jmg-2023-109203 |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.DF73F0A9 |
| Database: |
BASE |