家族性肥厚型心肌病大家系肌球蛋白结合蛋白C3基因突变筛查  

Mutation screening of cardiac myosin binding protein-C3 gene in a Chinese pedigree with familial hypertrophic cardiomyopathy

作　　者：冯建忠[1] 潘齐川[1] 王兵[1] 徐潮[2] 马修云[2] 孙逊[2] 潘春明[3] 赵双霞[3] 苏斌[3] 宋怀东[3] 

机构地区：[1]250013济南市卫生科技交流服务中心科技科 [2]青岛大学医学院附属威海医院内一科 [3]上海交通大学医学院附属瑞金医院医学基因组学国家重点实验室

出　　处：《中国医药》2012年第6期657-659,共3页China Medicine

基　　金：国家自然科学基金资助项目（81000039）;济南市科学技术发展计划项目（201101108）

摘　　要：目的 研究一汉族家族性肥厚型心肌病（FHCM）家系患者的致病基因突变位点,分析其基因型与表型关系.方法 收集到一规模较大的FHCM家系,共5代89位成员,采集到67份血样.用primerexperss 2.0软件设计引物扩增肌球蛋白结合蛋白C3（ MyBPC3）基因的各外显子及相邻内含子区,产物纯化后应用美国ABI PRISM 3700 DNA自动测序仪进行测序,用Autoassembler 2.0软件将测序结果与MyBPC3的基因组序列进行比较、分析.结果 该家系共14例患者（4例已去世,其中2例是年轻时猝死）,在世的10例患者左心室壁厚度均超过13 mm.符合常染色体显性遗传病的特点.经突变筛查,发现2处碱基改变,经检索国家生物技术信息中心单核苷酸多态性数据库,这些碱基改变均为多态性.结论 MyBPC3基因不是该家系的致病基因,反映了肥厚型心肌病的遗传异质性,需对其他可能的候选致病基因进行筛查.Objective To identify the disease-causing gene mutation and to investigate the genotype-pheno- type correlation in a Chinese pedigree with familial hypertrophic cardiomyopathy（FHCM）. Methods In this study we collected a large multigenerational Chinese family with FHCM. Total genome DNA was extracted from 67 subjects＇ peripheral leucocytes. The exons and boundary introns of cardiac myosin binding protein-C3 gene were ampli-fied by polymeras chain reation（PCR） and directly sequenced by ABI PRISM 3700 DNA sequencer. The mutation was examined. Results Fourteen family members had hypertrophic cardiomyopathy. Echocardiography showed all living affected individuals had a maximal left ventricular wall thickness of at least 13 mm. Two single nucleotide polymorphisms （SNP） were found and have been reported in NCBI SNP database. No mutation co-seperated with the disease was identified. Conclusions FHCM of this family is not caused by MyBPC3 mutation. Other genes should be screened.

关 键 词：心肌病 肥厚型 家族性 β肌球蛋白重链基因 突变 

分 类 号：R542.2[医药卫生—心血管疾病]