扩大 SCN8A 相关疾病的基因型-表型谱。
Expanding the genotype-phenotype spectrum in SCN8A-related disorders.
机构信息
Division of Neurology, Department of Pediatrics, BC Children's Hospital, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
Xenon Pharmaceuticals, 200-3650 Gilmore Way, Burnaby, BC, V5G 4W8, Canada.
出版信息
BMC Neurol. 2024 Jan 17;24(1):31. doi: 10.1186/s12883-023-03478-y.
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.
背景
SCN8A 相关疾病是一组由 SCN8A 致病变异引起的具有多种表现的疾病。在线孟德尔遗传数据库（OMIM）将其归类为发育性和癫痫性脑病 13、良性家族性婴儿癫痫 5 或伴有或不伴有小脑共济失调的认知障碍。
方法
本研究通过外显子组测序，对六个家系的八名个体的临床和基因结果进行了描述，这些个体均携带 SCN8A 致病性变异。
结果
临床表型范围从癫痫控制良好的正常发育到治疗抵抗性癫痫伴显著发育迟缓。在 SCN8A 中观察到三个新的和三个报道的变异。转染细胞的电生理分析显示患者 4 存在功能丧失变异。
结论
本研究扩展了 SCN8A 相关疾病的临床和基因型谱，并提供了新型 SCN8A 功能丧失变异的电生理结果。
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