Identification of the Tuberous Sclerosis Gene TSC1 on Chromosome 9q34
Marjon van Slegtenhorst, Ronald de Hoogt, Caroline Hermans, Mark Nellist, Bart Janssen, Senno Verhoef, Dick Lindhout, Ans van den Ouweland, Dicky Halley, Janet Young, Mariwyn Burley, Steve Jeremiah, Karen Woodward, Joseph Nahmias, Margaret Fox, Rosemary Ekong, John Osborne, Jonathan Wolfe, Sue Povey, Russell G. Snell, Jeremy P. Cheadle, Alistair C. Jones, Maria Tachataki, David Ravine, Julian R. Sampson, Mary Pat Reeve, Paul Richardson, Friederike Wilmer, Cheryl Munro, Trevor L. Hawkins, Tiina Sepp, Johari B. M. Ali, Susannah Ward, Andrew J. Green, John R. W. Yates, Jolanta Kwiatkowska, Elizabeth P. Henske, M. Priscilla Short, Jonathan H. Haines, Sergiusz Jozwiak, David J. Kwiatkowski- Multidisciplinary
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.