Nathan Routledge, Maxime Lammens, Reza Maroofian, Bakht Beland, David Murphy, Asif Mir, Zia Ullah, Javeria Reza Alvi, Tipu Sultan, Stephanie Efthymiou, Frank Bosmans, Henry Houlden
{"title":"Biallelic Truncating Variants in SCN3B Encoding Nav Channel Subunit β3 Lead to Neurodevelopmental Phenotype with and without Epilepsy and Ataxia.","authors":"Nathan Routledge, Maxime Lammens, Reza Maroofian, Bakht Beland, David Murphy, Asif Mir, Zia Ullah, Javeria Reza Alvi, Tipu Sultan, Stephanie Efthymiou, Frank Bosmans, Henry Houlden","doi":"10.1002/ana.78014","DOIUrl":null,"url":null,"abstract":"<p><p>SCN3B encodes the β3 auxiliary subunit, essential for voltage-gated Na<sup>+</sup> (Nav) channel trafficking and gating. Although SCN3B has been associated with cardiac disorders, a link with neurodevelopmental disorders (NDD) has not been established. Using a genotype-first approach, we identified homozygous truncating variants (c.281G>A-β3<sup>W94*</sup>, c.584 + 1G>A-β3<sup>S196*</sup>) in 2 consanguineous Pakistani families, leading to global developmental delay, intellectual disability and autism, with severe cognitive impairment, ataxia, and seizures in the case of β3<sup>W94*</sup>. Electrophysiological analysis revealed subtype-specific gating alterations on multiple brain Nav channel subtypes. This is the first report linking SCN3B mutations to NDD, expanding our understanding of Nav channelopathies. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":7.7000,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ana.78014","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
SCN3B encodes the β3 auxiliary subunit, essential for voltage-gated Na+ (Nav) channel trafficking and gating. Although SCN3B has been associated with cardiac disorders, a link with neurodevelopmental disorders (NDD) has not been established. Using a genotype-first approach, we identified homozygous truncating variants (c.281G>A-β3W94*, c.584 + 1G>A-β3S196*) in 2 consanguineous Pakistani families, leading to global developmental delay, intellectual disability and autism, with severe cognitive impairment, ataxia, and seizures in the case of β3W94*. Electrophysiological analysis revealed subtype-specific gating alterations on multiple brain Nav channel subtypes. This is the first report linking SCN3B mutations to NDD, expanding our understanding of Nav channelopathies. ANN NEUROL 2025.
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
