常染色体显性遗传成人多囊性肾病一个家系的遗传学分析及产前诊断  

Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease

作　　者：唐智华 郑春兰[1] 王文文[1] 何政霞 张婵丽 王艳[1] 马骞[1] 郭红军[1] Tang Zhihua;Zheng Chunlan;Wang Wenwen;He Zhengxia;Zhang Chanli;Wang Yan;Ma Qian;Guo Hongjun(Department of Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院妇科,郑州450052

出　　处：《中华医学遗传学杂志》2024年第9期1072-1076,共5页Chinese Journal of Medical Genetics

基　　金：河南省医学科技攻关项目省部共建项目(SBGJ202103081)。

摘　　要：目的探讨1个成人多囊性肾病(ADPKD)家系的临床表型及遗传学病因。方法选取2022年12月于郑州大学第一附属医院妇科就诊的1个ADPKD家系为研究对象。收集该家系的临床资料,应用全外显子组测序(WES)技术对先证者及其丈夫进行分析,对候选变异进行Sanger测序家系验证及生物信息学分析。本研究通过郑州大学第一附属医院医学伦理委员会的审查(伦理号:KS-2018-KY-36)。结果家系中胎儿超声检查提示双肾体积增大、实质回声增强。测序发现先证者携带PKD1基因c.11098C>T(p.R3700C)杂合变异,其丈夫携带c.11039T>C(p.F3680S)杂合变异,胎儿携带c.11098C>T(p.R3700C)和c.11039T>C(p.F3680S)复合杂合变异。根据美国医学遗传学与基因组学学会(ACMG)相关指南,二者均被判定为疑似致病性变异(PM1+PM2_Supporting+PP3,PM1+PM2_Supporting+PP3)。结论PKD1基因c.11098C>T(p.R3700C)与c.11039T>C(p.F3680S)复合杂合变异可能为上述胎儿的遗传学病因。上述发现为该家系的遗传咨询及产前诊断提供了线索。ObjectiveTo explore the clinical phenotype and genetic etiology for a Chinese pedigree affected with Autosomal dominant polycystic kidney disease(ADPKD).MethodsA pedigree with ADPKD diagnosed at the Department of Gynaecology of the First Affiliated Hospital of Zhengzhou University in December 2020 was selected as the study subject.Clinical data of the pedigree was collected,and whole exome sequencing(WES)was carried out for the proband.Candidate variants were verified by Sanger sequencing of the proband and her relatives.This study was approved by the First Affiliated Hospital of Zhengzhou University(Ethics No.KS-2018-KY-36).ResultsFetal ultrasonography showed increased volume and parenchymal echogenicity in both kidneys.The fetus was found to harbor c.11098C>T(p.R3700C)and c.11039T>C(p.F3680S)compound heterozygous variants of the PKD1 gene,which were respectively inherited from its mother and father.Based on the guidelines from the American College of Medical Genetics and Genomics(ACMG),both variants were predicted to be likely pathogenic(PM1+PM2_Supporting+PP3).ConclusionThe c.11098C>T(p.R3700C)and c.11039T>C(p.F3680S)compound heterozygous variants of the PKD1 gene probably underlay the ADPKD in the fetus.Above finding has provided guidance for the genetic counseling and prenatal diagnosis for this pedigree.

关 键 词：多囊性肾病 全外显子组测序 基因变异 产前诊断 

分 类 号：R714.5[医药卫生—妇产科学] R440[医药卫生—临床医学]