Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34
Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34
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DOI：
10.1126/science.277.5327.805
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发表时间：
1997-08-08
期刊：
影响因子：
56.9
通讯作者：
Kwiatkowski, DJ
中科院分区：
文献类型：
--
作者：
vanSlegtenhorst, M;deHoogt, R;Kwiatkowski, DJ
结节性硬化症（TSC）是一种常染色体显性遗传病，其特点是广泛发展的独特肿瘤称为错构瘤。tsc决定位点已定位到染色体9q34 （TSC1）和16p13 （TSC2）。TSC1基因是从一个包含至少30个基因的900千碱基区域中鉴定出来的。8.6千碱基的TSC1转录物被广泛表达并编码一个130千道尔的蛋白（错构体），该蛋白与一种功能未知的酵母蛋白具有同源性。在TSC1中发现了32个不同的突变，其中30个是截断的，在6个明显无关的患者中发现了一个突变（2105delAAAG）。在这六例中，在tsc相关的肾癌中发现了野生型等位基因的体细胞突变，这表明错构体具有肿瘤抑制作用。
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-assaciated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.