PDF(Pubmed)
Abstract：
BACKGROUND: SCN8A-related disorders are a group of variable conditions caused by pathogenic variations in SCN8A. Online Mendelian Inheritance in Man (OMIM) terms them as developmental and epileptic encephalopathy 13, benign familial infantile seizures 5 or cognitive impairment with or without cerebellar ataxia.
METHODS: In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing.
RESULTS: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4.
CONCLUSIONS: This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.
METHODS: In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing.
RESULTS: Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4.
CONCLUSIONS: This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.
摘要：
背景：SCN8A相关疾病是由SCN8A的致病变异引起的一组可变病症。在线孟德尔人遗传（OMIM）将其称为发育性和癫痫性脑病13，良性家族性婴儿癫痫发作5或有或没有小脑共济失调的认知障碍。
方法：在本研究中，我们描述了通过外显子组测序鉴定的来自6个SCN8A致病变异家族的8个个体的临床和遗传结果.
结果：临床发现范围从癫痫控制良好的正常发育到难治性癫痫的明显发育迟缓。在SCN8A中观察到三种新的和三种报道的变体。转染细胞中的电生理学分析揭示了患者4中的功能丧失变体。
结论：这项工作扩展了SCN8A相关疾病的临床和基因型谱，并提供了一种新型功能丧失SCN8A变体的电生理结果。
方法：在本研究中，我们描述了通过外显子组测序鉴定的来自6个SCN8A致病变异家族的8个个体的临床和遗传结果.
结果：临床发现范围从癫痫控制良好的正常发育到难治性癫痫的明显发育迟缓。在SCN8A中观察到三种新的和三种报道的变体。转染细胞中的电生理学分析揭示了患者4中的功能丧失变体。
结论：这项工作扩展了SCN8A相关疾病的临床和基因型谱，并提供了一种新型功能丧失SCN8A变体的电生理结果。
