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
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引用次数: 0
摘要
SCN3B编码β3辅助亚基，对电压门控Na+ (Nav)通道运输和门控至关重要。虽然SCN3B与心脏疾病有关，但与神经发育障碍（NDD）的联系尚未建立。采用基因型优先的方法，我们在2个巴基斯坦近亲家庭中发现了纯合截断变异体（c.281G> a -β3W94*, c.584 + 1G> a -β3S196*），导致全面发育迟缓、智力残疾和自闭症，并伴有严重的认知障碍、共济失调和癫痫。电生理分析揭示了多种脑Nav通道亚型特异性门控改变。这是第一个将SCN3B突变与NDD联系起来的报告，扩大了我们对Nav通道病变的理解。Ann neurol 2025。
Biallelic Truncating Variants in SCN3B Encoding Nav Channel Subunit β3 Lead to Neurodevelopmental Phenotype with and without Epilepsy and Ataxia.
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.
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