Identification of the Tuberous Sclerosis Gene <i>TSC1</i> on Chromosome 9q34

TLDR

Tuberous sclerosis complex is an autosomal dominant disorder marked by widespread hamartomas, with disease loci mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene, located in a 900‑kb region on 9q34, encodes an 8.6‑kb, 130‑kDa protein (hamartin) and harbors 32 mutations—mostly truncating—including a recurrent 2105delAAAG mutation in six patients, with a somatic mutation in a renal carcinoma indicating hamartin functions as a tumor suppressor.

Abstract

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-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.