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。

abstractsObjective: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.