MYOTONIC-DYSTROPHY MUTATION - AN UNSTABLE CTG REPEAT IN THE 3' UNTRANSLATED REGION OF THE GENE
MYOTONIC-DYSTROPHY MUTATION - AN UNSTABLE CTG REPEAT IN THE 3' UNTRANSLATED REGION OF THE GENE
复制标题
DOI：
10.1126/science.1546325
复制
发表时间：
1992-03-06
期刊：
影响因子：
56.9
通讯作者：
KORNELUK, RG
中科院分区：
文献类型：
--
作者：
MAHADEVAN, M;TSILFIDIS, C;KORNELUK, RG
强直性肌营养不良症(DM)是成人最常见的遗传性神经肌肉疾病，全球发病率为8000人中有1人。糖尿病是一种常染色体显性遗传性多系统疾病，以肌强直和进行性肌肉无力为主要特征。基因组和互补DNA探针映射到人类染色体19q13.3的10kb Eco RI基因组片段，已用于检测糖尿病患者的可变长度多态性。DM患者等位基因大小的增加现在被证明是由于DM候选基因的3‘非翻译区中三核苷酸CTG重复数的增加。随着疾病严重程度的增加(遗传预期)，三核苷酸重复的数量也会增加。几乎所有的DM病例(98%或258人中的253人)都显示出CTG重复区域的扩大。这些结果表明，DM主要是由产生特定CTG重复序列扩增的突变引起的。
Myotonic dystrophy (DM) is the most common inherited neuromuscular disease in adults, with a global incidence of 1 in 8000 individuals. DM is an autosomal dominant, multisystemic disorder characterized primarily by myotonia and progressive muscle weakness. Genomic and complementary DNA probes that map to a 10-kilobase Eco RI genomic fragment from human chromosome 19q13.3 have been used to detect a variable length polymorphism in individuals with DM. Increases in the size of the allele in patients with DM are now shown to be due to an increased number of trinucleotide CTG repeats in the 3' untranslated region of a DM candidate gene. An increase in the severity of the disease in successive generations (genetic anticipation) is accompanied by an increase in the number of trinucleotide repeats. Nearly all cases of DM (98 percent or 253 of 258 individuals) displayed expansion of the CTG repeat region. These results suggest that DM is primarily caused by mutations that generate an amplification of a specific CTG repeat.