Many studies have demonstrated the clinical utility and importance of epilepsy gene panel testing to confirm the specific aetiology of disease, enable appropriate therapeutic interventions, and inform accurate family counselling. Previously, SCN9A gene variants, in particular a c.1921A>T p.(Asn641Tyr) substitution, have been identified as a likely autosomal dominant cause of febrile seizures/febrile seizures plus and other monogenic seizure phenotypes indistinguishable from those associated with SCN1A, leading to inclusion of SCN9A on epilepsy gene testing panels. Here we present serendipitous findings of genetic studies that identify the SCN9A c.1921A>T p.(Asn641Tyr) variant at high frequency in the Amish community in the absence of such seizure phenotypes. Together with findings in UK Biobank these data refute an association of SCN9A with epilepsy, which has important clinical diagnostic implications.

许多研究已经证明了癫痫基因组检测的临床实用性和重要性，以确认疾病的特定病因，实现适当的治疗干预，并为准确的家庭咨询提供信息。以前，SCN9A基因变异，特别是 c.1921A>T p.(Asn641Tyr) 替代，已被确定为热性惊厥/热性惊厥加和其他与SCN1A相关的单基因癫痫表型无法区分的常染色体显性遗传原因，导致将SCN9A纳入癫痫基因检测组。在这里，我们介绍了鉴定SCN9A的遗传研究的偶然发现c.1921A>T p.(Asn641Tyr) 变异在阿米什社区中出现高频率变异，而没有这种癫痫发作表型。连同英国生物银行的研究结果，这些数据驳斥了SCN9A与癫痫的关联，这具有重要的临床诊断意义。