多个Wiskott-Aldrich综合征家系致病基因突变分析及产前诊断  

Gene mutation analysis of 11 Wiskott-Aldrich syndrome families and prenatal diagnosis

作　　者：徐若琛 贾竟[1] 赵振华[2] 冯乐丞 代启森 苗长青 张桢 孔祥东[2] 郑红[1] XU Ruochen;JIA Jing;ZHAO Zhenhua;FENG Lecheng;DAI Qisen;MIAO Changqing;ZHANG Zhen;KONG Xiangdong;ZHENG Hong(Department of Medical Genetics and Cell Biology,Basic Medical College,Zhengzhou University,Zhengzhou 450001;Genetic and Prenatal Diagnosis Center,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052)

机构地区：[1]郑州大学基础医学院医学遗传学与细胞生物学系,郑州450001 [2]郑州大学第一附属医院遗传与产前诊断中心,郑州450052

出　　处：《郑州大学学报(医学版)》2025年第2期238-241,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：国家自然科学基金面上项目(81571154);2023年郑州大学研究生自主创新项目。

摘　　要：目的:分析11个Wiskott-Aldrich综合征(WAS)家系的致病基因突变,并建立相应的产前诊断策略。方法:收集11个WAS家系的病史信息和临床资料。采集家系1~5、11中先证者(患儿)与母亲(妊娠期)外周静脉血,抽取胎儿羊水或绒毛样本,采集家系6~10中先证者(患儿)与母亲外周静脉血,应用二代基因测序、Sanger测序以及突变效应预测等对WAS基因的外显子区及侧翼序列进行分析,确定突变位点并进行产前诊断。结果:11个家系中先证者均有血小板减少、感染和出血等临床症状。共检出10种WAS基因致病突变,其中c.273G>A、c.361-2A>T、c.1183_1191del、c.331_332insCC为新发突变,致病性分析表明均具有致病性。产前诊断表明5个家系中的胎儿携带与先证者及其母亲相同的突变,决定终止妊娠,5个家系决定对先证者进行临床治疗,1个家系中的先证者及母亲携带c.946dupC移码突变,但胎儿基因检测正常,完成遗传咨询。结论:11个家系共发现10个WAS基因致病突变,其中4个突变为首次报道;应用二代基因测序明确WAS患者病因、进行产前诊断可避免有家族史的WAS家庭再次生育患儿。Aim:To analyze the pathogenic gene mutations of 11 families with Wiskott-Aldrich syndrome(WAS)and to conduct corresponding prenatal diagnosis strategies.Methods:Medical histories and clinical data were collected from 11 families with WAS.The peripheral venous blood samples from the probands(affected children)and their mothers in pedigrees 1-11 were collected,and fetal amniotic fluid or chorionic villus samples in pedigrees 1-5 and 11 were extracted,and next-generation gene sequencing(NGS),Sanger sequencing,and mutation effect prediction were performed to analyze the exonic and flanking sequences of the WAS gene,identify the mutation sites,and conduct prenatal diagnosis.Results:The probands in 11 families had exhibited significant clinical symptoms,including decreased platelet count,infections,and bleeding.Genetic sequencing identified 10 pathogenic mutations,among which,c.273G>A,c.361-2A>T,c.1183_1191del,and c.331_332insCC were newly reported.Prenatal diagnosis was performed for the affected families.In 5 families,the fetuses carried the same mutation as the proband and the mother,leading to a decision to terminate the pregnancy;another 5 families chose to treat the probands clinically;in 1 family,the proband and mother carried the c.946dupC frameshift mutation,but the fetal genetic test was normal,and genetic counseling was completed.Conclusion:Ten pathogenic mutations of WAS gene were found in 11 families,with 4 being reported for the first time.The use of NGS to identify the etiology of WAS patients and provide customized prenatal diagnosis is an effective method to prevent the recurrence of affected children in families with a history of WAS.

关 键 词：WISKOTT-ALDRICH综合征 WAS基因 基因突变 产前诊断 

分 类 号：R725.9[医药卫生—儿科] R758.23[医药卫生—临床医学]