儿童Rotor综合征临床特点及SLCO1B1和SLCO1B3基因突变分析  

Analysis of clinical feature and SLCO1B1 and SLC01B3 gene mutations in children with Rotor syndrome

作　　者：叶家卫 谭丽梅 杨峰霞 徐翼 李旭芳 YE Jiawei;TAN Limei;YANG Fengxia;XU Yi;LI Xufang(Department of Infectious Diseases,Guangzhou Women and Children s Medical Center,Guangzhou 510120,China)

机构地区：[1]广州市妇女儿童医疗中心感染性疾病科,广州510120

出　　处：《广州医药》2021年第6期1-5,共5页Guangzhou Medical Journal

摘　　要：目的对3例儿童Rotor综合征的临床特点及SLCO1B1和SLCO1B3基因突变分析,提高儿科医生对Rotor综合征的认识。方法收集广州市妇女儿童医疗中心2018年—2019年确诊的3例Rotor综合征患儿的临床资料,对患儿及其家系成员肝脏常见遗传代谢性疾病二代测序筛查并家系验证结果进行分析。结果患儿主要临床表现为反复或持续巩膜和(或)皮肤轻度黄染,实验室检查提示高直接胆红素血症。二代测序发现3例患儿均为SLCO1B1基因c.1738C>T纯合突变和SLCO1B3基因5号内含子区域大片段插入纯合突变。SLCO1B1基因和SLCO1B3基因2处纯合突变均进行了家系验证。文献报道的SLCO1B1基因c.1738C>T突变是无义突变,可以造成蛋白功能缺失;SLCO1B3基因的大片段插入突变虽暂未有文献收录或报道,但大片段的插入突变可引起移码突变而造成编码蛋白功能丧失。结论由于基因检测技术的不断进步,Rotor综合征不断被儿科医生所认识。SLCO1B1和SLCO1B3双基因纯合或复合杂合突变是3例Rotor综合征患儿的分子遗传基础。Objective To better understand Rotor syndrome(RS)in children,the clinical features and SLCO1B1 and SLC01B3 gene mutations were analyzed.Methods The clinical data of the 3 pediatric cases diagnosed in Guangzhou Women and Children s Medical Center between 2018 and 2019 was collected.Genomic DNA was extracted from the children and their family members,and subjected for second-generation sequencing to screen the known genes for liver genetic metabolic diseases.Then the detected mutations were confirmed by Sanger sequencing analysis.Results The main clinical manifestations were recurrent or persistent mild yellowish sclera and/or skin.Laboratory examinations showed hyperbilirubinemia with direct bilirubin elevating.Second generation sequencing showed that all 3 children were c.1738c>T homozygous mutations of SLCO1B1 gene and homozygous mutations of large fragment insertion in SLCO1B3 gene intron 5.Two homozygous mutations in SLCO1B1 gene and SLCO1B3 gene were verified in families.SLCO1B1 gene c.1738C>T mutation,a nonsense mutation reported in references,could lead to protein function loss.A large insertion mutation of SLCO1B3 gene could cause frame-shift mutation which might lead to protein function loss even though it was neither reported in the references nor recorded in SNP database.Conclusion Due to the progress in the clinical application of gene detection technology,RS has been recognized gradually by pediatricians.Homozygous mutations or compound heterozygous mutations simultaneously occurred in SLCO1B1 and SLCO1B3 gene were the molecular genetics base in these cases of RS.

关 键 词：ROTOR综合征 SLCO1B1基因 SLCO1B3基因 

分 类 号：R440[医药卫生—诊断学] R725.9[医药卫生—临床医学]