Miki T, Yamagata H, Ogihara T
Department of Geriatric Medicine, Osaka University Medical School.
Rinsho Shinkeigaku. 1995 Dec;35(12):1479-81.
The gene for myotonic dystrophy (DM) was found to be an expansion of an unstable CTG repeat located in the 3'-UTR of the putative protein kinase gene. In the general population 5 approximately 37 copies of the repeat are present, but in DM patients the repeat number varies from 50 up to thousands of copies. We have determined the copy number of the CTG repeat and made a haplotype using the closely linked markers to the CTG repeat in 93 Japanese DM families. The absolute linkage disequilibrium was observed in patients from both populations, between the DM gene and the linked markers. These data strongly suggest a common origin of Caucasian and Japanese DM alleles. The genetic analysis of apparently sporadic occurrence of DM in a family in which two asymptomatic members have been shown to have a number of repeats corresponding to premutation alleles, 44 and 46 CTG alleles. These data strongly suggest that (CTG) 19 approximately 37 may act as a predisposing allele for successive DM generations and that there is a premutation allele for DM, as predicted in a multistep model for etiology of this disorder.
强直性肌营养不良（DM）基因被发现是位于假定蛋白激酶基因3'-UTR的不稳定CTG重复序列的扩增。在一般人群中，该重复序列约有37个拷贝，但在DM患者中，重复序列的数量从50个到数千个不等。我们已经确定了93个日本DM家族中CTG重复序列的拷贝数，并使用与CTG重复序列紧密连锁的标记构建了单倍型。在这两个人群的患者中，DM基因与连锁标记之间均观察到完全连锁不平衡。这些数据强烈表明白种人和日本DM等位基因有共同起源。对一个家族中明显散发的DM进行遗传分析，该家族中有两名无症状成员被证明具有与前突变等位基因相对应的重复序列数量，即44和46个CTG等位基因。这些数据强烈表明，（CTG）19至37可能作为DM连续几代的易感等位基因，并且正如该疾病病因多步骤模型所预测的那样，存在DM的前突变等位基因。
