Au K S, Rodriguez J A, Rodriguez E, Dobyns W B, Delgado M R, Northrup H
Department of Pediatrics, University of Texas Medical School, Houston 77030, USA.
Hum Mutat. 1997;9(1):23-9. doi: 10.1002/(SICI)1098-1004(1997)9:1<23::AID-HUMU4>3.0.CO;2-Q.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder of benign tumor formation, hamartomata, and hamartias. TSC has been shown to be genetically heterogeneous, with one causative gene mapping to chromosome 9q (denoted TSC1) and at least one other gene on chromosome 16p (denoted TSC2). The TSC2 gene was recently cloned. We have tested 88 TSC probands with the TSC2 cDNA by Southern blotting searching for gross deletions/rearrangements/insertions. We detected two deletions and a rare intragenic polymorphic variant. This is a similar rate of mutation detection (2/88; 2.3%) to that in the original report (10/260/; 3.8%). The rare polymorphic variant was initially detected in the proband of a chromosome 9-linked multiplex TSC family. The polymorphism segregated with previously tested markers on chromosome 16 independently of the disease gene, verifying that the variation was unrelated to TSC status. We have also begun searching for subtle mutations by SSCA and direct sequencing. After screening three exons, we found two intragenic polymorphic variants. Both polymorphisms are common, making them useful for linkage studies in known affected families.
结节性硬化症（TSC）是一种常染色体显性遗传病，可形成良性肿瘤、错构瘤和发育异常。研究表明，TSC具有遗传异质性，其中一个致病基因定位于9号染色体（标记为TSC1），另一个致病基因至少定位于16号染色体（标记为TSC2）。TSC2基因最近已被克隆。我们通过Southern印迹法，用TSC2 cDNA检测了88例TSC先证者，以寻找大片段缺失/重排/插入。我们检测到两个缺失和一个罕见的基因内多态性变异。这一突变检出率（2/88；2.3%）与最初报告的检出率（10/260；3.8%）相似。这个罕见的多态性变异最初是在一个与9号染色体连锁的多重TSC家族的先证者中检测到的。该多态性与16号染色体上先前检测的标记独立分离，与疾病基因无关，证实该变异与TSC状态无关。我们也已开始通过单链构象多态性分析（SSCA）和直接测序寻找微小突变。在筛选了三个外显子后，我们发现了两个基因内多态性变异。这两种多态性都很常见，使其可用于已知患病家族的连锁研究。
