摘要
目的:探讨一例表现为无诱因惊厥发作、生长发育迟缓、血乳酸值升高的2月龄患儿的遗传学病因。方法:应用二代测序技术对患儿进行全外显子组和线粒体环基因测序,用Sanger测序对候选致病变异进行验证,依据美国医学遗传学及基因组学学会相关指南进行致病性分析。检索PubMed、万方数据库和中国知网数据库中FARS2变异所致的联合氧化磷酸化缺乏症14型(COXPD14)的病例报道,总结其临床特征及基因变异谱。结果:全外显子组测序提示患儿携带FARS2基因c.925G>A(p.G309S)和c.405C>A(p.H135Q)复合杂合变异;Sanger测序证实这两个变异分别遗传自母亲和父亲。其中c.925G>A为HGMD数据库已收录的致病变异,c.405C>A预测为疑似致病变异。检索文献另发现30例COXPD14患者,其FARS2变异类型包括错义变异、剪接变异、读码框内碱基缺失和编码区微缺失。结论:COXPD14临床表现以发育迟缓(96%)、癫痫发作(97%)和乳酸升高(96%)最为经典。FARS2基因c.925G>A(p.G309S)和c.405C>A(p.H135Q)复合杂合变异是本例患儿的发病原因。
Objective To explore the genetic etiology for an infant featuring convulsive status epilepticus,developmental delay and elevated plasma lactate.Methods Whole exome sequencing and mitochondrial D-loop sequencing were carried out for the infant.Candidate variants were verified by Sanger sequencing.Previously reported FARS2 gene variants were searched from the PubMed,Wanfang and CNKI databases.Results The infant was found to harbor compound heterozygous variants of the FARS2 gene,namely c.925G>A(p.G309S)and c.405C>A(p.H135Q),which were inherited from its mother and father,respectively.The former has been recorded by the HGMD as a pathogenic variant,whilst the latter was predicted to be likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics.A total of 30 COXPD14 cases were retrieved from the literature,with common mutations including missense variants,in-frame deletions,splice-site variants and large deletions.Conclusion The common manifestations of COXPD14 have included developmental delay(96%),status epilepticus(97%)and increased lactic acid(96%).The compound heterozygous variants of the FARS2 gene probably underlay the disorder in this child.
作者
马健
张洪伟
律玉强
高敏
王东
盖中涛
刘毅
Ma Jian;Zhang Hongwei;Lyu Yuqiang;Gao Min;Wang Dong;Gai Zhongtao;Liu Yi(Jinan Pediatric Research Institute,Children′s Hospital Affiliated to Shandong University,Jinan,Shandong 250022,China;Epilepsy Center,Children′s Hospital Affiliated to Shandong University,Jinan,Shandong 250022,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第12期1393-1397,共5页
Chinese Journal of Medical Genetics
基金
济南市卫生健康委员会科技计划(20190228)。
