Variants in ATP6V0C are associated with Dravet‐like developmental and epileptic encephalopathy
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Le résumé fourni par la source
OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy. Diagnosis is clinical, but ~90% of patients have pathogenic variants in SCN1A. ATP6V0C has recently been proposed as a novel candidate gene for epilepsy, with or without developmental delay. Here we describe two adult patients with a clinical diagnosis of DS associated with ATP6V0C variants. METHODS: Patients with developmental and epileptic encephalopathies were evaluated by physicians who are experts in DS, and their clinical diagnosis was correlated with genetic findings. A subgroup of those patients with DS but without known genetic causes were evaluated through gene panels, whole exome sequencing, and chromosome microarray. Phenotype was determined by pediatric and adult chart reviews, interviews, and physical examinations. RESULTS: Of 753 patients with DS, two unrelated individuals with classic features of DS during childhood and adulthood were identified with heterozygous de novo missense variants in ATP6V0C (c.319G > C, p.(Gly107Arg) and c.284C > T, p.(Ala95Val), respectively). Both variants were absent in normal populations and computational prediction algorithms suggested deleterious effects on protein structure and/or function. No disease-causing variants in other genes previously associated with DS were found. SIGNIFICANCE: Here we describe two adult patients with Dravet-like syndrome and pathogenic/likely pathogenic variants in ATP6V0C. We propose that abnormal ATP6V0C function can, at the severe end of the clinical spectrum, be associated with Dravet-like phenotype. This is relevant, as these patients would not qualify for disease-modifying antisense nucleotide or gene therapies targeting SCN1A.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Variants in <i>ATP6V0C</i> are associated with Dravet‐like developmental and epileptic encephalopathy
- Date Crossref
- 14/03/2025
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Toronto Krembil Brain Institute pays non établi dans la noticeUniversité ou école supérieure
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Toronto Western Hospital pays non établi dans la noticeÉtablissement de santé
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Ontario Brain Institute pays non établi dans la noticeOrganisation à but non lucratif
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Universidad Europea de Madrid Epilepsy and Neurogenetics Unit pays non établi dans la noticeUniversité ou école supérieure
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University of Southern Denmark Department of Regional Health Research pays non établi dans la noticeUniversité ou école supérieure
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Epilepsy Action pays non établi dans la noticeOrganisation à but non lucratif
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Epilepsy Foundation pays non établi dans la noticeOrganisation à but non lucratif
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University of Copenhagen Department of Drug Design and Pharmacology pays non établi dans la noticeUniversité ou école supérieure
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Danish Gas Technology Centre (Denmark) pays non établi dans la noticeEntreprise
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Hospital for Sick Children pays non établi dans la noticeÉtablissement de santé
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SickKids Foundation pays non établi dans la noticeOrganisation à but non lucratif
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Centre for Applied Genomics pays non établi dans la noticeStructure de recherche
Krembil Brain Institute — University of Toronto, Toronto Western Hospital et Ontario Brain Institute, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.