一个家族性肥厚型心肌病大家系致病基因的定位研究  

Positional cloning of disease-causing gene in a Chinese pedigrees with familial hypertrophic cardiomyopathy

作　　者：潘齐川 徐潮[2] 冯建忠 田小晔 潘春明[3] 苏斌[3] 杜雪 

机构地区：[1]卫生科技交流服务中心科技科,济南市250013 [2]山东大学附属省立医院内分泌科 [3]上海瑞金医院医学基因组学国家重点实验室

出　　处：《中国医药》2013年第11期1527-1530,共4页China Medicine

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

摘　　要：目的识别一汉族家族性肥厚型心肌病（FHCM）家系的致病基因，分析其基因型与表型关系。方法收集到一个规模较大的FHCM家系，共5代89位成员，采集外周血标本，抽提基因组DNA。应用美国ABI PRISM 3700 DNA自动测序仪进行全基因组扫描，连锁分析确定初步致病基因的初步区域后，进一步进行精细定位和单倍型分析，搜索候选基因并明确致病基因。结果该家系共14例患者（4例已经去世，其中2例是年轻时猝死），在世的10例患者的左心室壁厚度均超过13mm。该家系遗传方式符合常染色体显性遗传病的特点，通过全基因组扫描和连锁分析，在微卫星标记D1$249处获得最大概率对数值，为3．45（重组率θ=0．15）。通过精细定位将致病基因所在位置确定为一号染色体长臂3区2带（1q32），该区域中含有肌钙蛋白T基因（TNNT2）。结论该家系的致病基因位于染色体1q32，TNNT2基因位于该区域，是重要的候选基因。Objective To identify the disease-causing gene and to investigate the genotype-phenotype cor- relation in a Chinese pedigree with familial hypertrophic cardiomyopathy （FHCM）. Methods In this study, a five- generation family that consisted of 89 individuals with FHCM was identified. Total genome DNA was extracted from 67 subjects＇ peripheral leucocytes. A genome-wide screening was carried out using micro-satellite markers on ABI PRISM 3700 DNA sequencer. A linkage analysis was performed using the MLINK program. Results Fourteen fam- ily members had hypertrophic cardiomyopathy. Analysis by echocardiography showed all living affected individuals had a maximal left-ventricular-wall thickness of at least 13 mm. A two-point LOD score of 3.45 （θ = 0.15）, sugges- tive of linkage, was initially obtained with microsatellite marker D1S249. The FHCM causing gene, cardiac troponin T gene was located in this area. Conclusions The disease locus is mapped to chromosome 1q32 in this family. As one of the aetiological genes for FHCM, it is reasonable to screen for mutations in the cardiac troponin T gene.

关 键 词：心肌病 肥大性 家族性 肌钙蛋白T基因 全基因组扫描 连锁分析 

分 类 号：R542.2[医药卫生—心血管疾病]