Kass S, MacRae C, Graber H L, Sparks E A, McNamara D, Boudoulas H, Basson C T, Baker P B, Cody R J, Fishman M C
Department of Genetics, Harvard Medical School, Boston, Massachussetts 02115.
Nat Genet. 1994 Aug;7(4):546-51. doi: 10.1038/ng0894-546.
Longitudinal evaluation of a seven generation kindred with an inherited conduction system defect and dilated cardiomyopathy demonstrated autosomal dominant transmission of a progressive disorder that both perturbs atrioventricular conduction and depresses cardiac contractility. To elucidate the molecular genetic basis for this disorder, a genome-wide linkage analysis was performed. Polymorphic loci near the centromere of chromosome 1 demonstrated linkage to the disease locus (maximum multipoint lod score = 13.2 in the interval between D1S305 and D1S176). Based on the disease phenotype and map location we speculate that gap junction protein connexin 40 is a candidate for mutations that result in conduction system disease and dilated cardiomyopathy.
对一个患有遗传性传导系统缺陷和扩张型心肌病的七代家族进行的纵向评估表明,一种进行性疾病以常染色体显性方式遗传,该疾病既扰乱房室传导又降低心脏收缩力。为了阐明这种疾病的分子遗传基础,进行了全基因组连锁分析。1号染色体着丝粒附近的多态性位点显示与疾病位点连锁(在D1S305和D1S176之间的区间,最大多点连锁值 = 13.2)。基于疾病表型和图谱位置,我们推测缝隙连接蛋白连接蛋白40是导致传导系统疾病和扩张型心肌病的突变候选基因。