PDHA1基因移码突变致丙酮酸脱氢酶E1-α缺乏症1例并文献复习  

Pyruvate dehydrogenase E1-alpha deficiency caused by frame-shift mutation of PDHA1 gene:a case report and literature review

作　　者：叶福玲 童光磊 李司南 李红 陈露露 易昕 YE Fuling;TONG Guanglei;LI Sinan;LI Hong;CHEN Lulu;YI Xin(Physiatry Department,Anhui Provincial Children's Hospital,Hefei,Anhui 230041,China)

机构地区：[1]安徽省儿童医院康复科,安徽合肥230041

出　　处：《安徽医药》2025年第3期611-614,共4页Anhui Medical and Pharmaceutical Journal

摘　　要：目的分析1例由PDHA1基因移码突变所致丙酮酸脱氢酶E1-α缺乏症病儿的临床表型及遗传学特点,为该病的临床诊断和遗传咨询提供参考依据。方法收集2021年7月至2022年1月病儿的临床资料,采集病儿及其正常表型的父母外周血样,提取全基因组DNA,应用二代测序技术对全外显子组基因进行变异检测、生物信息学预测分析确定致病基因,通过Sanger测序对亲代进行验证。结果测序结果显示病儿PDHA1基因发生c.576_577del(p.L193lfs*7)杂合变异,经Sanger验证病儿父母未检出该变异,为一新发变异。根据美国医学遗传学与基因组学学会(ACMG)的指南预测c.576_577del为致病性变异。结论PDHA1基因c.576_577del(p.L193lfs*7)变异为病儿的遗传学病因,新变异的发现丰富了PDHA1基因变异谱,为进一步研究丙酮酸脱氢酶缺乏症的致病机制提供了临床资料和遗传资源。Objective To analyze the clinical manifestation and genetic features of a child with pyruvate dehydrogenase E1-alpha deficiency caused by frame-shift mutation of PDHA1 gene,and to provide reference for clinical diagnosis and genetic consultation.Meth⁃ods The clinical data of the child from July 2021 to January 2022 were collected.The peripheral blood samples of the child and the parents with normal phenotypes were taken for the whole genome DNA.Next-generation sequencing was used to detect variations of whole exome genes,bioinformatics predictive analysis to determine pathogenic genes,and Sanger sequencing to verify parents.Results Sequencing results showed c.576_577del(p.L193lfs*7)heterozygous variation in PDHA1 gene.Sanger sequencing verified that the mutation was not detected in the parents,so it was a new mutation.According to the guideline of the American College of Medical Genetics and Genomics(ACMG),c.576_577del was predicted to be the pathogenic variation.Conclusion PDHA1 gene c.576_577del(p.L193LFS*7)mutation is the genetic cause of the disease.This case enriches the variation spectrum of PDHA1 gene and provides clinical data and genetic resources for further research on the pathogenesis of pyruvate dehydrogenase deficiency.

关 键 词：丙酮酸脱氢酶复合物缺乏症 丙酮酸脱氢酶E1亚基alpha1(PDHA1)基因 发育迟滞 移码突变 全外显子组测序 生酮膳食 

分 类 号：R725.9[医药卫生—儿科]