一个遗传性癫痫伴热性惊厥附加症家系的临床表型及 SCN1A基因变异分析

目的:分析1个遗传性癫痫伴热性惊厥附加症(genetic epilepsy with febrile seizures plus,GEFS+)家系的临床表型及遗传特征进行分析。方法:收集先证者及其家系成员的临床资料并提取外周血DNA,对先证者采用高通量测序以确定潜在的变异位点,对其家系成员采用Sanger测序进行验证。...

Analysis of clinical phenotype and SCN1A gene variant in a pedigree affected with genetic epilepsy with febrile seizuresCSCD

Objective To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+ ). Methods Clinical data of the proband and his family members were collected.Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members. Results The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+ . Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+ ), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c. 4522T>A (p.Tyr1508Asn) of the SCN1A gene.Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%. Conclusion The c. 4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree.The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene. © 2021 West China University of Medical Sciences. All rights reserved.