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。

abstractsObjective: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.