2例DGUOK基因相关线粒体DNA耗竭综合征的临床及基因变异特征

Clinical and genetic variation characteristics of two children with mitochondrial DNA depletion syndrome caused by DGUOK gene variants

目的 探讨2例线粒体DNA耗竭综合征(MDS)患儿的临床特征与基因变异特点。方法 回顾性分析2例肝脑型MDS患儿的临床资料及基因检测结果,并进行相关文献复习。结果 先证者1为2日龄男婴,临床表现为严重代谢性酸中毒,肝功能异常及脑白质病变等。全外显子测序提示DGUOK基因存在c.534G>A(p.T178X)纯合无义变异,产生含有178个氨基酸的截短蛋白。Sanger测序验证其父母和姐姐均携带该位点杂合变异。先证者2为1日龄男婴,主要临床表现为黄疸,肝功能受损。全外显子测序提示DGUOK基因存在c.313C>T(p.R105X)纯合变异,生成含有105个氨基酸的截短蛋白,变异遗传自父母。根据美国医学遗传学与基因组学学会指南,2例变异均评估为致病性(PVS1+PM2+PM3)。结论 DGUOK基因的纯合变异可能是导致本文报道2例患儿发病的遗传学病因,拓展了DGUOK基因变异谱。

Objective To investigate the clinical features and gene variation characteristics of two children with mitochondrial DNA depletion syndrome(MDS).Methods The clinical data and genetic test results of 2 children were retrospectively analyzed,and the related literature was reviewed.Results The proband 1 was a 2-days-old boy with severe metabolic acidosis,abnormal liver function and white matter lesions.The whole exon sequencing indicated that there was homozygous nonsense variation of c.534G>A(p.T178X)in DGUOK gene,which resulted in the production of truncated protein containing 178 amino acids.Sanger sequencing verified that both parents and sisters carried the heterozygous variation of this locus.The proband 2 is a 1-day-old boy,whose main manifestations are jaundice and liver function damage.The whole exon sequencing indicates that there is a homozygous mutation of c.313C>T(p.R105X)in DGUOK gene,which resulted in a truncated protein containing 105 amino acids,and the mutation is inherited from his parents.According to the guidelines of American College of Medical Genetics and Genomics(ACMG),both mutations were evaluated as pathogenic(PVS1+PM2+PM3).Conclusion The homozygous variation of DGUOK gene may be the genetic cause of 2 cases reported in this paper,which expands the spectrum of DGUOK gene variants.