一个X-连锁无丙种球蛋白血症家系的BTK基因突变研究  

Genetic study of an X-linked agammaglobulinemia pedigree caused by an BTK mutation

作　　者：韦晨曦 杨如镜[2] 袁小庚 于世辉[3] 秦建平 田新显 张暋 Wei Chenxi;Yang Rujing;Yuan Xiaogeng;Yu Shihui;Qin Jianping;Tian Xinxian;Zhang Min(Zhengzhou KingMed Center for Clinical Laboratory,Zhengzhou,Henan 450016,China;The Third Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Guangzhou KingMed Center for Clinical Laboratory,Guangzhou,Guangdong 510030,China)

机构地区：[1]郑州金域临床检验中心有限公司,450016 [2]郑州大学第三附属医院(河南省妇幼保健院),450052 [3]广州金域医学检验中心有限公司,510030

出　　处：《中华医学遗传学杂志》2021年第11期1081-1086,共6页Chinese Journal of Medical Genetics

基　　金：广州产业领军人才集聚工程项目(CXLJTD-201603)。

摘　　要：目的分析一个丙种球蛋白缺乏症患病家系的遗传学病因,协助临床确诊并对家族生育进行指导。方法收集家系内患者及家族成员的临床资料,检测家系成员的免疫球蛋白水平、淋巴细胞分类及亚群;应用二代测序技术进行全外显子检测,确认基因变异并对其进行分级;使用Sanger测序验证变异位点并检测家系内的变异情况。结果该家系内发现BTK新的致病基因突变c.1627T>C(p.Ser543Pro),表型与变异存在家系共分离;人群数据库未见收录。突变位于激酶域,区域内未发现良性变异,生物学信息分析预测为有害。结论BTK基因c.1627T>C(p.Ser543Pro)为致病变异,是导致该家系X-连锁无丙种球蛋白血症的原因,可以据此为家族成员提供生育指导及产前诊断。Objective To explore the genetic pathogenesis of X-linked agammaglobulinemia in two patients for clinical diagnosis and family counseling.Methods Data was collected from the patients’family including clinical information,blood immunoglobulin level,as well as classification and subgrouping of B lymphocytes.Gene mutations were screened by whole exome sequencing(WES)through next-generation sequencing(NGS),the result was verified with Sanger sequencing.Results A BTK c.1627T>C(p.Ser543Pro)variant was found in the pedigree.The phenotype and variant have co-segregated in the pedigree.The variant was not found in population database.The variant has affected in the kinase domain which contained no benign variants and is harmful as predicted through bioinformatic analysis.Conclusion BTK c.1627T>C(p.Ser543Pro)is a pathogenic variant contributing to X-linked agammaglobulinemia in this pedigree.Above finding has provided reproduction guidance for this family.

关 键 词：X-连锁先天性无丙种球蛋白血症 BTK基因 致病变异 全外显子测序 

分 类 号：R725.9[医药卫生—儿科]