一个家族性肝内胆汁淤积症家系的临床表型与遗传学分析  

Phenotype and genetic analysis of a pedigree affected with progressive familial intrahepatic cholestasis

作　　者：吴庆华[1] 马贝贝 杨赛赛 梅世月[1] 麻希洋 孔祥东[1] 史惠蓉[1] Wu Qinghua;Ma Beibei;Yang Saisai;Mei Shiyue;Ma Xiyang;Kong Xiangdong;Shi Huirong(Center of Genetics and Prenatal Diagnosis,Department of Obstetrics and Gynecology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,妇产医学部,450052

出　　处：《中华医学遗传学杂志》2019年第8期789-793,共5页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(81701497).

摘　　要：目的探讨一个家族性肝内胆汁淤积症家系的临床表型及遗传学病因。方法应用二代测序技术,对该家系的先证者行胆汁淤积症相关基因突变筛查,并对2例患者及其父母行PCR扩增和直接双向测序进行验证。结果该家系中的2例患者临床主要特征为黄疸、皮肤瘙痒和生长发育迟缓。二代测序检测提示先证者携带编码胆汁酸盐输出泵蛋白的ABCB11基因c.2494C > T(p.Arg832Cys)和c.3223C >T(p.Gln1075*)复合杂合突变,经PCR扩增及测序可见其有相同症状的妹妹携带该复合杂合突变,分别来自父亲和母亲。结论该家系为ABCB11基因突变导致的进行性家族性肝内胆汁淤积症2型,ABCB11基因c.3223C>T(p.Gln1075*)无义突变导致蛋白质翻译的提前终止。明确了该家系的遗传学病因,对家系中后代再发风险的预测有重要的指导意义。Objective To explore the genetic etiology for a pedigree affected with progressive familial intrahepatic cholestasis (PFIC). MethodsTarget sequence capture and next generation sequencing (NGS) were applied for the proband. PCR and Sanger sequencing were used to verify the suspected mutation in his sister with similar symptoms and his parents. Results The proband and his sister manifested after birth with symptoms including jaundice, pruritus and developmental retardation. NGS has identified compound heterozygous mutations of ABCB11 gene, which encodes bile salt export pump protein (BSEP), namely c. 2494C>T (p.Arg832Cys) and c. 3223C>T (p.Gln1075*), in the proband, which were inherited from his father and mother respectively. His sister carried the same compound mutations. Conclusion Based on the phenotype and genetic testing, the patients were diagnosed as PFIC2 caused by mutation of the ABCB11 gene. The c. 3223C>T is a novel nonsense mutation which may cause premature termination of translation. Above results have enriched the spectrum of ABCB11 mutations and provided new evidence for the molecular basis of PFIC, which also facilitated genetic counseling for this pedigree.

关 键 词：进行性家族性肝内胆汁淤积症 二代测序 ABCB11基因 单基因病诊断 

分 类 号：R575[医药卫生—消化系统]