ATP6V0A4基因变异致原发性远端肾小管酸中毒患儿1例的临床特征及遗传学分析  

Clinical and genetic analysis of a patient with primary distal renal tubular acidosis due to variants of ATP6V0A4 gene

作　　者：李玛丽 胡姝雯 刘超[1] 宋娜 汪治华[1] Li Mali;Hu Shuwen;Liu Chao;Song Na;Wang Zhihua(Department of Endocrinology,Genetics and Metabolism,Xi′an Children′s Hospital,Xi′an,Shaanxi 710003,China)

机构地区：[1]西安市儿童医院内分泌遗传代谢科,西安710003

出　　处：《中华医学遗传学杂志》2023年第10期1275-1279,共5页Chinese Journal of Medical Genetics

基　　金：陕西省重点研发计划(2023-YBSF-065);西安市科技计划(21YXYJ0013);西安市儿童医院院内课题(2022F04)。

摘　　要：目的分析1例原发性远端肾小管酸中毒(dRTA)患儿的临床及遗传学特征。方法选取2021年4月因"食纳差10 d,哭闹2 d"就诊于西安市儿童医院的1例原发性dRTA患儿作为研究对象,收集患儿的临床资料。应用全外显子组测序及Sanger测序进行变异分析及家系验证。结果患儿为1月18日龄男性,临床主要表现为食纳差、烦躁哭闹、体重不增及脱水。患儿实验室检查提示代谢性酸中毒、电解质紊乱(高氯、低钾)、反常性碱性尿及贫血;泌尿系彩色多普勒超声提示双肾髓质钙盐沉积。基因检测发现患儿ATP6V0A4基因存在父源性c.1363dupA(p.M455NfsX14)和母源性c.2257C>T(p.Q753X)复合杂合变异。根据美国医学遗传学与基因组学学会相关变异标准与指南,c.1363dupA(p.M455NfsX14)评级为致病性变异(PVS1+PM3+PM2_Supporting),c.2257C>T(p.Q753X)评级为致病性变异(PVS1+PM3+PM2_Supporting)。结论ATP6V0A4基因c.1363dupA(p.M455NfsX14)和c.2257C>T(p.Q753X)变异考虑是患儿致病的原因。c.2257C>T(p.Q753X)变异的发现拓展了ATP6V0A4基因的变异谱。Objective To explore the clinical features and genetic etiology of a patient with primary distal renal tubular acidosis(dRTA).Methods A child who was diagnosed with primary dRTA at the Xi'an Children′s Hospital in April 2021 due to poor appetite and persistent crying was selected as the study subject.Clinical data of the patient was collected.Whole exome sequencing(WES)was carried out for the child.Candidate variants were validated by Sanger sequencing of his family members.Results The child,a 1-month-and-18-day male,had featured poor appetite,persistent crying,poor weight gain and dehydration.Laboratory examination has suggested metabolic acidosis,hyperchloremia,hypokalemia,abnormal alkaline urine and anemia.Ultrasonographic examination of the urinary system revealed calcium deposition in renal medulla.DNA sequencing revealed that he has harbored compound heterozygous variants of the ATP6V0A4 gene,namely c.1363dupA(p.M455NfsX14)and c.2257C>T(p.Q753X),which were respectively inherited from his father and mother.Based on the guidelines from the American College of Medical Genetics and Genomics,both variants were classified as pathogenic(PVS1+PM3+PM2_Supporting).Conclusion The compound heterozygous variants of c.1363dupA(p.M455NfsX14)and c.2257C>T(p.Q753X)of the ATP6V0A4 gene probably underlay the pathogenesis of primary dRTA in this patient.Discovery of the c.2257C>T(p.Q753X)variant has expanded the mutational spectrum of the ATP6V0A4 gene.

关 键 词：酸中毒 肾小管性 ATP6V0A4基因 基因变异 代谢性酸中毒 低钾血症 儿童 

分 类 号：R726.9[医药卫生—儿科]