Identification of the Tuberous Sclerosis Gene TSC1 on Chromosome 9q34

• Published in: Science (American Association for the Advancement of Science) 1997-08, Vol.277 (5327), p.805-808
• Main Authors: van Slegtenhorst, Marjon, de Hoogt, Ronald, Hermans, Caroline, Nellist, Mark, Janssen, Bart, Verhoef, Senno, Lindhout, Dick, Van den Ouweland, Ans, Halley, Dicky, Young, Janet, Burley, Mariwyn, Jeremiah, Steve, Woodward, Karen, Nahmias, Joseph, Fox, Margaret, Ekong, Rosemary, Osborne, John, Wolfe, Jonathan, Povey, Sue, Snell, Russell G., Cheadle, Jeremy P., Jones, Alistair C., Tachataki, Maria, Ravine, Dave, Sampson, Julian R., Reeve, Mary Pat, Richardson, Paul, Wilmer, Frierderike, Munro, Cheryl, Hawkins, Trevor L., Sepp, Tiina, Johari B. M. Ali, Ward, Susannah, Green, Andrew J., John R. W. Yates, Kwiatkowska, Jolanta, Elizabeth P. H enske, Short, M. Priscilla, Haines, Jonathan H., Jozwiak, Sergiusz, Kwiatkowski, David J.
• Format: Article
• Language: English
• Subjects: Alleles; Amino Acid Sequence; Biological and medical sciences; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 9 - genetics; Coding; Complementary DNA; Exons; Family (Sociological Unit); Genes; Genes, Tumor Suppressor; Genetic aspects; Genetic disorders; Genetic mutation; Genetic screening; Genomics; Hamartoma; Humans; Medical disorders; Medical sciences; Microsatellite Repeats; Molecular Sequence Data; Molecular Weight; Mutation; Neurology; Patients; Polymerase Chain Reaction; Proteins - chemistry; Proteins - genetics; Proteins - physiology; Repressor Proteins - genetics; Repressor Proteins - physiology; Transcripts (Written Records); Tuberous sclerosis; Tuberous Sclerosis - genetics; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins; Tumors; Tumors of the nervous system. Phacomatoses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.277.5327.805

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.