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n 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。n 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。n “,”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 n 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.n 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.n