Epstein N D, Fananapazir L, Lin H J, Mulvihill J, White R, Lalouel J M, Lifton R P, Nienhuis A W, Leppert M
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Circulation. 1992 Feb;85(2):635-47. doi: 10.1161/01.cir.85.2.635.
Recently, two families with hypertrophic cardiomyopathy have been shown to have mutations in the cardiac beta-myosin heavy chain gene (beta-MHC) located on the long arm of chromosome 14.
We have performed linkage analysis of five newly ascertained pedigrees with more than 50 chromosomal markers detecting polymorphisms. Our findings confirm the linkage to beta-MHC gene locus on chromosome 14 in one family (LOD score, 4.50) and suggest linkage to the same gene in another kindred. Chromosome 14 markers were not linked to the disease gene in the other three kindreds, however, and a test for genetic heterogeneity was statistically significant. Moreover, markers for the beta-MHC gene identified affected individuals who were recombinants with respect to this gene and the disease phenotype in these three kindreds.
These results provide conclusive evidence that hypertrophic cardiomyopathy in separate families is caused by mutations in disease genes at two or more locations in the genome.
最近，已证明两个肥厚型心肌病家族在位于14号染色体长臂上的心脏β-肌球蛋白重链基因（β-MHC）存在突变。
我们对5个新确定的家系进行了连锁分析，使用了50多个检测多态性的染色体标记。我们的研究结果证实了一个家族中与14号染色体上的β-MHC基因座存在连锁关系（对数优势分数，4.50），并提示另一个家族中也与该基因存在连锁关系。然而，在其他三个家族中，14号染色体标记与疾病基因没有连锁关系，并且遗传异质性检验具有统计学意义。此外，β-MHC基因的标记在这三个家族中识别出了与该基因和疾病表型发生重组的受影响个体。
这些结果提供了确凿证据，表明不同家族中的肥厚型心肌病是由基因组中两个或更多位置的疾病基因突变引起的。
