THE MOLECULAR-GENETICS OF TUBEROUS SCLEROSIS
THE MOLECULAR-GENETICS OF TUBEROUS SCLEROSIS
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DOI：
10.1093/hmg/3.suppl_1.1477
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发表时间：
1994-01-01
影响因子：
3.5
通讯作者：
HARRIS, PC
中科院分区：
文献类型：
--
作者：
SAMPSON, JR;HARRIS, PC
脑硬化症（TSC）是一种常染色体显性遗传性状，其特征是广泛发展的良性肿瘤，归类为错构瘤，并经常与癫痫发作和智力低下。生长的斑片状分布和病灶性质表明，它们可能是由两次打击过程中肿瘤抑制基因失活引起的。在过去的2年里，研究设计调查生殖细胞和体细胞TSC突变已经借给支持这一假设。对TSC相关错构瘤的分析表明，已知含有TSC基因的9号和16号染色体区域的杂合性丢失，与体细胞“二次打击”突变的发生一致。使用脉冲场凝胶电泳的平行研究已经确定了代表16p13.3处“首发”突变的组成缺失，从而快速鉴定了致病基因之一TSC 2。有趣的是，TSC2的产物，tuberin，与GT3激活蛋白rap1GAP有一个序列同源性区域，这表明它在调节细胞生长中的作用可能是一种机制。
Tuberous sclerosis (TSC) is an autosomal dominant trait characterized by the widespread development of benign tumours classified as hamartoma, and is often associated with seizures and mental retardation. The patchy distribution and focal nature of the growths suggests that they might result from inactivation of a tumour suppressor gene by a two-hit process. Over the last 2 years, studies designed to investigate both germline and somatic TSC mutations have lent support to this hypothesis. Analysis of TSC-associated hamartomas has shown loss of heterozygosity for the regions of chromosomes 9 and 16 known to harbour TSC genes, consistent with the occurrence of somatic 'second-hit' mutations. Parallel investigations using pulse field get electrophoresis have identified constitutional deletions representing 'first-hit' mutations at 16p13.3, leading to the rapid identification of one of the causative genes, TSC2. Intriguingly, the TSC2 product, tuberin, has an area of sequence homology with the GTPase activating protein rap1GAP, suggesting a possible mechanism for its role in regulating cellular growth.