Dravet综合征SCNIA基因新突变及遗传咨询

摘要:目的对2 例癫痫伴精神运动发育迟缓的患儿进行遗传学病因分析,旨在为患儿治疗及其家庭遗传咨询、生育指导提供依据。方法提取2例患儿及 其父母外周血基因组DNA并采用全外显子测序技术进行检测,按照美国医学遗传学与基因组学学会(ACMG,2015)标准进行致病性分析,通过Sanger测序验证致病变异。结果全外显子测序结果发现,2例患儿电压门控性钠离子通道a1亚单位基因(SCNIA)基因存在c.5354T>C(p.11785T)和c.4380T>A(p.Y1460* )新发de novo杂合突变,分别评估变异为可疑致病、致病突变位点,Sanger测序验证了该突变并确认双方父母相应位点均为野生型。结论结 合临床和基因诊断信息,2例患儿均被诊断为常染色体显性遺传病Dravet综合征,明确患儿的致病原因对于合理治疗方案的制定及其家庭的优生优育、遗传咨询具有重要的意义。

Identification of novel mutations in SCNIA gene for Dravet syndrome and genetic counseling

Abstract: Objective We aim to explore the genetic etiology of two children with epilepsy and psychomotor retardation, and provide the genetic basis of therapy, genetic counseling and reproductive guidance for the children and their families. Methods The genomic DNA was extracted from the peripheral blood of the two children and their parents and tested by whole-exome sequencing technology.The pathogenicity analysis was performed according to the standards of the American College of Medical Genetics and Genomics ( AC-MG, 2015). Sanger sequencing was applied to confim these pathogenic mutations. Results W hole exome sequencing revealed that two heterozygous de novo likely pathogenic mutations c. 5354T>C (p.I1785T) and c.4380T>A(p. Y1460 * ) in voltage-gated sodium channel al subunit gene ( SCNIA ) was present in the two probands. Sanger sequencing confirmed the mutations were present in the two children and bothwere wild-type in their parents. Conclusion The two children were diagnosed as Dravet syndrome according to clinical and genetic diagnostic information. This diagnosis should be of great value for the reasonable therapy regimen and genetic counselingfor their families.