四例Dubin-Johnson综合征患者的临床表型与遗传学分析  

The phenotypes and genotypes of four patients with Dubin-Johnson syndrome

作　　者：吴庆华[1] 马贝贝 杨赛赛 焦智慧[1] 陈心 任淑敏[1] 陈义兵[1] 史惠蓉[1] 孔祥东[1] Wu Qinghua;Ma Beibei;Yang Saisai;Jiao Zhihui;Chen Xin;Ren Shumin;Chen Yibing;Shi Huirong;Kong Xiangdong(Center of Genetics and Prenatal Diagnosis,the First Affiliated Hospital of Zhengzhou University,Zhengzhou,Henan 450052,China;Department of Obstetrics and Gynecology,the Central Hospital of Puyang,Puyang,Henan 457000,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,郑州450052 [2]濮阳市人民医院妇产科,河南457000

出　　处：《中华医学遗传学杂志》2022年第10期1065-1069,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4例临床不明原因胆红素升高患者的临床表型特点与分子遗传学病因。方法收集患者的临床资料;提取患者基因组DNA,应用二代测序技术对患者行遗传代谢性肝病相关基因变异筛查,采用PCR和Sanger测序对可疑致病的基因变异位点行验证检测。结果4例患者均为男性,主要临床表现为皮肤眼白发黄,无其他特殊不适症状;肝功能检查示胆红素升高,以结合胆红素升高为主,余肝功能指标无异常。基因检测提示4例患者均为ABCC2基因双杂合变异,分别为c.3011C>T(p.T1004I)和c.3541C>T(p.R1181X)、c.1177C>T(p.R393W)和c.2077G>A(p.G693R),c.2125T>C(p.W709R)和c.4025C>A(p.S1342Y),c.2443C>T(p.R815X)和c.2556del(p.G853Efs*7),其中c.3011C>T、c.2443C>T和c.2556del为既往文献未报道过的变异。结论经基因检测明确这4例患者均为ABCC2基因变异所致的Dubin-Johnson综合征。本研究检测到了3个ABCC2基因的新变异,增加了该疾病的基因变异谱。该综合征预后好,明确病因学诊断后可极大减轻患者精神心理负担并避免过度诊疗,同时对家系遗传咨询具有重要的指导意义。Objective To explore the genetic etiology in four patients with hyperbilirubinemia,and discuss the correlation between clinical characteristics and molecular basis.Methods The data of clinical manifestation and auxiliary examinations were collected.Genomic DNA of the four patients was extracted and analyzed by next-generation sequencing using the panel including genes involved in hereditary metabolic liver diseases.Suspected variants were verified by Sanger sequencing.Results All of the four patients were males with normal liver enzymes.It was revealed that all the patients had heterozygous variants,among which c.3011C>T,c.2443C>T and c.2556del were the variants which have not been reported previously.Conclusion All of the patients were diagnosed as Dubin-Johnson syndrome(DJS)caused by ABCC2 gene variants.The novel variants add to the spectrum of genetic variant of the disease.Because of the favorite prognosis,precise diagnosis can greatly reduce the psychological pressure of patients and avoid excessive treatments.At the same time,it could provide pertinent genetic counseling for the families.

关 键 词：黄疸 ABCC2基因 二代测序 DUBIN-JOHNSON综合征 

分 类 号：R575[医药卫生—消化系统]