The genetic basis of tuberous sclerosis

Gomez, 1991, Phenotypes of the tuberous sclerosis complex with a revision of diagnostic criteria, Ann. New York Acad. Sci., 615, 1, 10.1111/j.1749-6632.1991.tb37742.x Gunther, 1935, The genetics of epiloia, J. Genet., 31, 413, 10.1007/BF02982409 Northrup, 1993, Variability of expression in tuberous sclerosis, J. Med. Genet., 30, 41, 10.1136/jmg.30.1.41 Smalley, 1994, Phenotypic variation of tuberous sclerosis in a single extended kindred, J. Med. Genet., 31, 761, 10.1136/jmg.31.10.761 Sampson, 1989, Genetic aspects of tuberous sclerosis in the west of Scotland, J. Med. Genet., 26, 28, 10.1136/jmg.26.1.28 Osborne, 1991, Epidemiology of tuberous sclerosis, Ann. New York Acad. Sci., 615, 125, 10.1111/j.1749-6632.1991.tb37754.x Yates, 1997, Female germline mosaicism in tuberous sclerosis confirmed by molecular genetic analysis, Hum. Mol. Genet., 6, 2265, 10.1093/hmg/6.13.2265 Povey, 1994, Two loci for tuberous sclerosis: one on 9q34 and one on 16p13, Ann. Hum. Genet., 58, 107, 10.1111/j.1469-1809.1994.tb01881.x 1993, Identification and characterization of the tuberous sclerosis gene on chromosome 16, Cell, 75, 1305, 10.1016/0092-8674(93)90618-Z 1997, Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34, Science, 277, 805, 10.1126/science.277.5327.805 Maheshwar, 1996, Comparative analysis and genomic structure of the tuberous sclerosis 2 (TSC2) gene in human and pufferfish, Hum. Mol. Genet., 5, 131, 10.1093/hmg/5.1.131 Kobayashi, 1997, Identification of a leader exon and a core promoter for the rat tuberous sclerosis 2 (Tsc2) gene and structural comparison with the human homolog, Mamm. Genome, 8, 554, 10.1007/s003359900502 Kobayashi, 1995, cDNA structure, alternative splicing and exon–intron organization of the predisposing tuberous sclerosis (Tsc2) gene of the Eker rat model, Nucleic Acids Res., 23, 2608, 10.1093/nar/23.14.2608 Kim, 1995, Cloning, developmental expression, and evidence for alternative splicing of the murine tuberous sclerosis (TSC2) gene product, Cell. Mol. Biol. Res., 41, 515 Olsson, 1996, Expression and differential splicing of the mouse TSC2 homologue, Mamm. Genome, 7, 212, 10.1007/s003359900057 Harris, 1995, Autosomal dominant polycystic kidney disease: molecular analysis, Hum. Mol. Genet., 4, 1745, 10.1093/hmg/4.suppl_1.1745 Michalet, 1997, Dynamic molecular combing: stretching the whole human genome for high resolution studies, Science, 277, 1518, 10.1126/science.277.5331.1518 Brook-Carter, 1994, Deletion of the TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease—a contiguous gene syndrome, Nat. Genet., 8, 328, 10.1038/ng1294-328 Sampson, 1997, Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene, Am. J. Hum. Genet., 61, 843, 10.1086/514888 Verhoef, 1995, Somatic mosaicism and clinical variation in tuberous sclerosis complex, Lancet, 345, 202, 10.1016/S0140-6736(95)90213-9 Wilson, 1996, Novel mutations detected in the TSC2 gene from both sporadic and familial TSC patients, Hum. Mol. Genet., 5, 249, 10.1093/hmg/5.2.249 van Bakel, 1997, Mutations in the TSC2 gene: analysis of the complete coding sequence using the protein truncation test (PTT), Hum. Mol. Genet., 6, 1409, 10.1093/hmg/6.9.1409 Jones, 1997, Molecular genetic and phenotypic analysis reveals differences between TSC1 and TSC2 associated familial and sporadic tuberous sclerosis, Hum. Mol. Genet., 6, 2155, 10.1093/hmg/6.12.2155 Maheshwar, 1997, The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for mis-sense mutations in tuberous sclerosis, Hum. Mol. Genet., 6, 1991, 10.1093/hmg/6.11.1991 Au, 1998, Germline mutational analysis of the TSC2 gene in 90 tuberous sclerosis patients, Am. J. Hum. Genet., 62, 286, 10.1086/301705 Jobert, 1997, Deletion of 11 amino acids in tuberin associated with severe tuberous sclerosis phenotypes: evidence for a new essential domain in the first third of the protein, Eur. J. Hum. Genet., 5, 280, 10.1159/000484778 Eker, 1961, A dominant gene for renal adenomas in the rat, Nature, 189, 858, 10.1038/189858b0 Kobayashi, 1995, A germline insertion in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer, Nat. Genet., 9, 70, 10.1038/ng0195-70 Yeung, 1994, Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene, Proc. Natl. Acad. Sci. U. S. A., 91, 11413, 10.1073/pnas.91.24.11413 Yeung, 1997, Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis, Am. J. Pathol., 151, 1477 Kobayashi, 1997, Transgenic rescue from embryonic lethality and renal carcinogenesis in the Eker rat model by introduction of a wild-type Tsc2 gene, Proc. Natl. Acad. Sci. U. S. A., 94, 3990, 10.1073/pnas.94.8.3990 Jin, 1996, Suppression of tumorigenicity by the wild-type tuberous sclerosis 2 (Tsc2) gene and its C-terminal region, Proc. Natl. Acad. Sci. U. S. A., 93, 9154, 10.1073/pnas.93.17.9154 Wienecke, 1995, Identification of tuberin, the tuberous sclerosis-2 product. Tuberin possesses specific Rap1GAP activity, J. Biol. Chem., 270, 16409, 10.1074/jbc.270.27.16409 Wienecke, 1996, Co-localisation of the TSC2 product tuberin with its target Rap1 in the Golgi apparatus, Oncogene, 13, 913 Xiao, 1997, The tuberous sclerosis 2 gene product, tuberin, functions as a Rab5 GTPase activating protein (GAP) in modulating endocytosis, J. Biol. Chem., 272, 6097, 10.1074/jbc.272.10.6097 Soucek, 1997, Role of the tuberous sclerosis gene-2 product in cell cycle control, J. Biol. Chem., 272, 29301, 10.1074/jbc.272.46.29301 Green, 1994, Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients, Nat. Genet., 6, 193, 10.1038/ng0294-193 Green, 1994, The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor, Hum. Mol. Genet., 3, 1833, 10.1093/hmg/3.10.1833 Carbonara, 1994, 9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene, Hum. Mol. Genet., 3, 1829, 10.1093/hmg/3.10.1829 Cavenee, 1983, Expression of recessive alleles by chromosomal mechanisms in retinoblastoma, Nature, 305, 779, 10.1038/305779a0 Knudson, 1971, Mutation and cancer: statistical study of retinoblastoma, Proc. Natl. Acad. Sci. U. S. A., 68, 820, 10.1073/pnas.68.4.820 Henske, 1997, Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumours, Am. J. Pathol., 151, 1639 Sepp, 1996, Loss of heterozygosity in tuberous sclerosis hamartomas, J. Med. Genet., 33, 962, 10.1136/jmg.33.11.962 Henske, 1996, Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions, Am. J. Hum. Genet., 59, 400 Henske, 1995, Loss of heterozygosity in the tuberous sclerosis (TSC2) region of chromosome 16p13 occurs in sporadic as well as TSC-associated renal angiomyolipomas, Genes Chromosomes Cancer, 13, 295, 10.1002/gcc.2870130411 Green, 1996, Clonality of tuberous sclerosis hamartomas shown by non-random X-chromosome inactivation, Hum. Genet., 97, 240, 10.1007/BF02265273 Carbonara, 1996, Apparent preferential loss of heterozygosity at TSC2 over TSC1 chromosomal region in tuberous sclerosis hamartomas, Genes Chromosomes Cancer, 15, 18, 10.1002/(SICI)1098-2264(199601)15:1<18::AID-GCC3>3.0.CO;2-7 Webb, 1991, Non-penetrance in tuberous sclerosis, J. Med. Genet., 28, 417, 10.1136/jmg.28.6.417