摘要目的 筛查家族性原发性胆汁性胆管炎(PBC)患者资料,利用全外显子组测序寻找PBC家系患者的共有低频突变,初步探讨其发病机制. 方法 收集2005年至2016年西京医院确诊的PBC患者资料,筛查其一级亲属自身抗体并明确诊断.提取2个高发家系中的PBC患者和正常对照的DNA进行全外显子组测序,筛选家系患者共有的低频突变. 结果 共计筛查435例PBC患者及其946例一级亲属资料,其中18例(1.90％)一级亲属也被诊断为PBC,共分布在16个家系(3.68％)中.全外显子组测序结果显示2个家系7名患者共同的低频突变包括16个单核苷酸多态性和2个插入缺失标记,其中ANO2 (rs17788563)可能与PBC的发病相关. 结论 PBC患者群体中存在高度聚集的家系患者,其具有共同的低频突变位点,其位点可能参与了PBC的发病.

abstractsObjective Screening of patients with familial primary biliary cholangitis by using wholeexome sequence to find common low-frequency mutations and to explore its pathogenesis.Methods The confirmed data of PBC patients diagnosed in Xijing hospital from 2005 to 2016 were collected,and their firstdegree relatives' autoantibodies were screened for diagnosis.DNA extraction from PBC patients and normal controls in two high-incidence families was performed for whole-exome sequencing,and the low-frequency mutations in the family were screened.Results A total of 435 PBC patients and 946 first-degree relatives were screened,and 18 (1.90％) first-degree relatives were also diagnosed with PBC,which was distributed in 16 families (3.68％).The whole-exome sequencing results showed that the common low-frequency mutations of 7 patients in 2 families consisted of 16 single nucleotide polymorphisms and 2 InDel markers,of which ANO2(rs17788563) may be correlated to the pathogenesis of PBC.Conclusion There is high-incidence of PBC in the family members of PBC patients with low-frequency mutation sites and their sites may be involved in the pathogenesis of PBC.