Krajinovic M, Pinamonti B, Sinagra G, Vatta M, Severini G M, Milasin J, Falaschi A, Camerini F, Giacca M, Mestroni L
International Centre for Genetic Engineering and Biotechnology, Ospedale Maggiore, Trieste, Italy.
Am J Hum Genet. 1995 Oct;57(4):846-52.
Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology, characterized by impaired myocardial contractility and ventricular dilatation. The disorder is an important cause of morbidity and mortality and represents the chief indication for heart transplantation. Familial transmission is often recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal dominant inheritance. In order to understand the molecular genetic basis of the disease, a large six-generation kindred with autosomal dominant FDC was studied for linkage analysis. A genome-wide search was undertaken after a large series of candidate genes were excluded and was then extended to two other families with autosomal dominant pattern of transmission and identical clinical features. Coinheritance of the disease gene was excluded for > 95% of the genome, after 251 polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22, with a maximum multipoint lod score of 4.2. There was no evidence of heterogeneity. The FDC locus was placed in the interval between loci D9S153 and D9S152. Several candidate genes for causing dilated cardiomyopathy map in this region.
特发性扩张型心肌病是一种病因不明的心肌疾病，其特征为心肌收缩功能受损和心室扩张。该病症是发病和死亡的重要原因，也是心脏移植的主要指征。常可见家族性遗传（家族性扩张型心肌病，即FDC），大多呈常染色体显性遗传。为了解该疾病的分子遗传学基础，对一个具有常染色体显性FDC的六代大家系进行了连锁分析。在排除了一系列候选基因后，进行了全基因组搜索，随后又扩展到另外两个具有常染色体显性遗传模式且临床特征相同的家系。在分析了251个多态性标记后，排除了疾病基因与基因组中95%以上区域的共遗传。发现9号染色体q13-q22存在连锁，最大多点对数优势分数为4.2。没有异质性的证据。FDC基因座位于D9S153和D9S152基因座之间的区间。该区域有几个导致扩张型心肌病的候选基因。
