DNA2基因变异所致进行性眼肌麻痹伴线粒体DNA缺失症6型1例患儿的临床特征及遗传学分析

Clinical features and genetic analysis of child with Progressive external ophthalmoplegia with mitochondrial DNA deletions,autosomal dominant 6 due to variant of DNA2 gene

目的探讨1例常染色体显性遗传的进行性眼肌麻痹伴线粒体DNA缺失症6型(PEOA6)患儿的遗传学病因。方法选取2023年8月7日就诊于宁波大学附属妇女儿童医院的1例PEOA6患儿作为研究对象,回顾性分析患儿的临床资料。对患儿进行全外显子组测序(WES),并对候选变异进行Sanger测序家系验证。本研究通过宁波大学附属妇女儿童医院医学伦理委员会的审查(伦理号:EC2020-048)。结果患儿为7岁女性,表现为四肢肌肉痛、肌无力、血清肌酸激酶水平明显升高、先天性膈疝和反复呼吸道感染。WES检测提示患儿携带DNA2基因c.1590G>C(p.L530F)杂合错义变异,Sanger测序验证其为新发变异。根据美国医学遗传学和基因组学学会相关指南评级为可能致病性变异(PS2+PM2_Supporting+PP3)。结论DNA2基因c.1590G>C(p.L530F)新发变异可能是PEOA6患儿的遗传学病因。

ObjectiveTo explore the genetic etiology for a child with Progressive external ophthalmoplegia with mitochondrial DNA deletions,autosomal dominant 6(PEOA6).MethodsA child who had attended the Women and Children′s Hospital Affiliated to Ningbo University on 7 August,2023 was selected as the study subject.Clinical data of the child were analyzed retrospectively.The child and her parents were subjected to whole exome sequencing(WES),and candidate variant was verified by Sanger sequencing and bioinformatic analysis.This study was approved by Medical Ethics Committee of the Women and Children′s Hospital Affiliated to Ningbo University(Ethics No.EC2020-048).ResultsThe child,a 7-year-old female,had presented with limb muscle pain,amyosthenia,significantly increased creatine kinase,congenital diaphragmatic hernia and recurrent respiratory tract infections.WES revealed that she has harbored a heterozygous c.1590G>C(p.L530F)variant of the DNA2 gene,which was verified to have a de novo origin by Sanger sequencing.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),the c.1590G>C was rated as a likely pathogenic variant(PS2+PM2_Supporting+PP3).ConclusionThe c.1590G>C(p.L530F)variant of the DNA2 gene probably underlay the PEOA6 in this child.