一个良性家族性新生儿惊厥家系的临床及基因变异分析CSCD

目的分析一个中国良性家族性新生儿惊厥(benign familial neonatal convulsions,BFNC)家系的临床特点,鉴定该家系的致病基因突变类型。方法收集2020年2月在宣城市中心医院新生儿科就诊的一个BFNC家系的临床资料和外周血样DNA,进行全外显子测序,筛选出的致病基因突变位点,采用Sanger测序法对每个家系成员的目标位点进行验证。结果该BFNC家系共9名成员,有4例受累者,其中男性3例、女性1例,起病年龄均在新生儿期,4~6月内惊厥发作停止,1例在1~2岁内复发1次。基因检测分析发现先证者KCNQ2基因第5外显子c.810G>A(p.W270X)杂合无义突变,该突变国内外文献均无报道。经Sanger测序验证,患儿哥哥、母亲及外公均携带该变异,该变异在该家庭中与疾病共分离。结论家系受累者均在新生儿期发病,预后良好,符合BFNC临床发病特点。KCNQ2基因无义突变C.810G>A(p.W270X)是该家系发病的遗传学基础,此发现拓宽了导致BFNC的KCNQ2基因突变谱。

Clinical and genetic analysis of a Chinese pedigree affected with benign familial neonatal convulsionCSCD

Objective To analyze the clinical phenotype and genetic variant in a Chinese pedigree affected with benign familial neonatal convulsion (BFNC). Methods Clinical data and peripheral blood samples of the pedigree were obtained with informed consent. Whole exome sequencing (WES) was carried out for the proband. Candidate variants were verified by Sanger sequencing. Results The pedigree comprised 9 individuals, among whom 4 were affected, including 3 males and 1 female. All patients had developed seizures during the neonatal period, which had ceased in 4 to 6 months. One patient had recurrence in between 1 and 2 years old. Genetic testing has identified a novel nonsense c. 810G> A (p. W270X) variant in exon 5 of the KCNQ2 gene, which has co-separated with the BFNC phenotype in the pedigree. Conclusion The patients from this pedigree have conformed to the diagnosis of BFNC with good prognosis, which was in keeping with previously reported cases. The heterozygous c. 810G>A (p. W270X) nonsense variant of the KCNQ2 gene probably underlay the pathogenesis of BFNC in this pedigree, which has expanded the mutational spectrum of the disease. © 2022 West China University of Medical Sciences. All rights reserved.