BBS7基因突变致Bardet-Biedl综合征胎儿/引产儿的基因诊断:两例报道  

Genetic diagnosis for fetal Bardet-Biedl syndrome caused by BBS7 gene mutations:report of two cases

作　　者：李博红 谢建生 耿茜 刘洋 徐志勇 李素丽 Li Bohong;Xie Jiansheng;Geng Qian;Liu Yang;Xu Zhiyong;Li Suli(Medical Genetics Laboratory,Shenzhen Maternity and Child Healthcare Hospital,The First School of Clinical Medicine,Southern Medical University,Shenzhen 518048,China)

机构地区：[1]南方医科大学第一临床医学院,深圳市妇幼保健院医学遗传中心,518084

出　　处：《中华围产医学杂志》2020年第6期380-386,共7页Chinese Journal of Perinatal Medicine

基　　金：深圳市科技创新委员会基础研究项目(JCYJ20170413092818116)。

摘　　要：目的对临床疑诊Bardet-Biedl综合征(Bardet-Biedl syndrome,BBS)的胎儿及引产儿各1例进行遗传学诊断,为BBS的产前诊断提供参考。方法病例1于2018年10月在深圳市妇幼保健院行产前检查,孕18周+1超声检查提示胎儿双肾实质回声增强,双足六趾,疑诊BBS,要求行产前遗传学基因诊断。病例2于2016年8月孕26周+4时在本院行产前超声检查,提示胎儿双侧肾脏明显增大,回声增强,双手、双足六指(趾),疑诊BBS。孕妇及其家属选择引产终止妊娠,并要求对引产胎儿行基因诊断。病例1于孕19周+6行羊膜腔穿刺留取羊水标本,病例2留取引产胎儿脐带组织,同时留取父母外周血标本,行全外显子组测序及生物信息学分析,并对高通量测序结果进行Sanger测序验证。结果(1)病例1胎儿:BBS7基因存在遗传自父亲的c.718G>A(p.Gly240Ser)突变(可能致病),以及遗传自母亲的c.497C>A(p.Ala166Asp)突变(可能致病)。(2)病例2引产胎儿:BBS7基因存在遗传自父亲的c.1002delT(p.N335Ifs*47)突变(已知致病),以及遗传自母亲的c.728G>A(p.Cys243Tyr)突变(可能致病)。这3个可能致病突变尚未检索到相关报道,经生物信息学软件预测为有害突变,经多物种蛋白序列比对,3个突变位点均具有保守性。结论BBS7基因突变导致的BBS胎儿可表现为双肾回声增强,双肾增大以及轴后多指(趾)畸形;全外显子组测序可为BBS的产前诊断及家系遗传咨询提供参考。Objective To summarize the genetic diagnosis of two fetuses with clinically suspected Bardet-Biedl syndrome(BBS)and to provide information for genetic counseling and prenatal diagnosis of BBS.Methods Case one had prenatal care on October 2018 in Shenzhen Maternity and Child Healthcare Hospital and was clinically suspected of fetal BBS as bilateral renal parenchyma echo enhancement as well as polydactyly(six toes on each foot)were shown on ultrasonic examination at 18+1 gestational weeks.Case two was another suspected fetal BBS for enlarged kidneys with echo enhancement as well as polydactyly(six fingers and toes on each hand and foot)on ultrasonic examination at 26+4 gestational weeks on August 2016 and the parent requested for termination.Parents of both cases requested for genetic analysis.Amniotic fluid sample was obtained in case one at 19+6 weeks through amniocentesis,and umbilical cord specimen of case two and peripheral blood samples of the parents were collected.Genetic analysis of the fetuses and their parents was performed using exon capture and next-generation sequencing and the results were validated using Sanger sequencing.Results Case one carried paternally inherited c.718G>A(p.Gly240Ser)(possible pathogenic)mutation and maternally inherited c.497C>A(p.Ala166Asp)(possible pathogenic)mutation in BBS7 gene.While one paternally inherited mutation c.1002delT(p.N335Ifs*47)(pathogenic)and one maternally inherited heterozygous mutation c.728G>A(p.Cys243Tyr)(possible pathogenic)were identified in BBS7 gene of case two.The three unreported missense mutations were predicted to be harmful by bioinformatics software and the mutation sites were conservative after comparing with multiple species-based protein sequences.Conclusions Enlarged kidneys with echo enhancement and polydactyly may indicated a BBS fetus caused by BBS7 gene mutation.Whole exome sequencing could provide relevant information for prenatal diagnosis and genetic counseling in these cases.

关 键 词：BARDET-BIEDL综合征 细胞支架蛋白质类 衔接蛋白质类 信号转导 突变 基因检测 超声检查 产前 

分 类 号：R440[医药卫生—诊断学] R714.5[医药卫生—临床医学]