Schönberger Jost, Kühler Leif, Martins Elisabete, Lindner Tom H, Silva-Cardoso Jose, Zimmer Michael
Department of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Grombühlstr. 12, 97080, Würzburg, Germany.
Hum Genet. 2005 Dec;118(3-4):451-7. doi: 10.1007/s00439-005-0064-2. Epub 2005 Oct 14.
Inherited dilated cardiomyopathy (DCM) is a genetically and phenotypically very heterogeneous disease. DCM is caused by mutations in multiple genes encoding proteins that are involved in force generation, force transmission, energy production and several signalling pathways. Thus, the pathophysiology of heart failure is complex and not yet fully understood. Familial forms of DCM let the way to identify new key proteins by positional cloning and to study respective pathomechanisms that are critical for normal cardiac function, but may not have been correlated with heart disease before. Here we report a three-generation pedigree including 16 individuals affected by dilated cardiomyopathy without additional phenotypes. The pedigree is consistent with autosomal-dominant inheritance and age-related penetrance. A genome-wide linkage analysis excluded linkage to all known DCM genes and loci, whereas several close markers on chromosome 7q22.3-31.1 segregated with the disease (maximum logarithm of odds score, 4.20 at D7S471 and D7S501). The disease causing mutation lies in a 9.73 Mb interval between markers D7S2545 and D7S2554 that contains no known cytoskeletal genes. Coding exons of the candidate genes LAMB1, LAMB4 and PIK3CG were screened but no mutations were identified.
遗传性扩张型心肌病（DCM）是一种在遗传和表型上都非常异质性的疾病。DCM由多个编码参与力量产生、力量传递、能量产生及多种信号通路的蛋白质的基因突变引起。因此，心力衰竭的病理生理学很复杂，尚未完全了解。家族性DCM为通过定位克隆鉴定新的关键蛋白以及研究对正常心脏功能至关重要但之前可能未与心脏病相关联的各自发病机制提供了途径。在此，我们报告一个三代家系，其中16名个体患有扩张型心肌病且无其他表型。该家系符合常染色体显性遗传及年龄相关的外显率。全基因组连锁分析排除了与所有已知DCM基因和位点的连锁关系，而7号染色体q22.3 - 31.1上的几个紧密标记与疾病共分离（最大优势对数得分，在D7S471和D7S501处为4.20）。致病突变位于标记D7S2545和D7S2554之间的9.73 Mb区间内，该区间不包含已知的细胞骨架基因。对候选基因LAMB1、LAMB4和PIK3CG的编码外显子进行了筛选，但未发现突变。
