摘要：

Tuberous sclerosis (TSC) is an autosomal dominant genetic disorder in which about two-thirds of all patients present without any evidence of prior family history. It has variable but generally high penetrance, and mosaicism has been documented. Linkage analysis indicates that two genes cause TSC, both of which are now known. TSC1 on chromosome 9q34 was recently indentified, encodes a 130 kDa protein of unknown function, and its mutational spectrum consists nearly exclusively of truncating point, insertion, and deletion mutations. TSC2 on 16p13 encodes an alternatively spliced 200 kDa protein which may have GTPase activating activity for the rap1 and rab5 GTPases, and its mutational spectrum consists of large genomic deletions, and small truncating and missense mutations. Many lesions from TSC patients have been shown to have undergone allele loss (LOH) consistent with a two hit mechanism fitting the tumor suppressor gene model. However, some of the myriad manifestations of TSC may be due to haploinsufficiency without need for a second hit. Although benign hamartomas are characteristic of TSC, they rarely progress to malignancy, this event occurring only in renal angiomyolipomas.

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