Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-27T06:10:28.491Z Has data issue: false hasContentIssue false
  • English
  • Français

Tuberous Sclerosis: Between Genetic and Physical Analysis

Published online by Cambridge University Press:  01 August 2014

D.J.J. Halley
D.J.J. Halley*
Affiliation:
Department of Clinical Genetics, Erasmus Universityand University Hospital, Rotterdam, The Netherlands
*
Department of Clinical Genetics, Erasmus Universityand University Hospital, P.O. BOX 1738, 3000 DR Rotterdam, The Netherlands

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder with extensive clinical variability. Present estimates of the prevalence of TSC suggest that it may exceed 1:6,000. New mutations are frequent, as about 2/3 of all cases are apparently sporadic. Locus heterogeneity has been established, with one gene on chromosome 9q34 (TSC1) and the other on chromosome 16p13.3 (TSC2). The majority of TSC2 mutations are propably subtle alterations. In some cases, somatic and germline mosaicism might be explanations for intrafamilial phenotypic variation and apparent non penetrance. A role of the predicted protein product tuberin in growth suppression would be in agreement with allelic losses observed in tumors of TSC patients. Studies on tuberin using antibodies raised against various parts of the protein can be expected to provide insight into its normal and impaired function.

Keywords

Tuberous Sclerosis Complex (TSC)TSC2 gene
Type
Research Article
Information
Acta geneticae medicae et gemellologiae: twin research , Volume 45 , Issue 1-2 , April 1996 , pp. 63 - 75
Copyright
Copyright © The International Society for Twin Studies 1996

References

REFERENCES

1. Gomez, MR: Tuberous sclerosis, ed. 2 New York, Raven, 1988.Google ScholarPubMed
2. Hunt, A, Lindenbaum, RH: Tuberous sclerosis: A new estimate of prevalence within the Oxford region. J Med Genet 1984; 21: 272–277.Google Scholar
3. Osborne, JP, Fryer, A, Webb, D: Epidemiology of tuberous sclerosis. Ann NY Acad Sci 1991; 615: 125–127.CrossRefGoogle ScholarPubMed
4. Van Baal, JG, Fleury, P, Brummelkamp, WH: Tuberous sclerosis and the relation with renal angiomyolipoma: A genetic study on the clinical aspects. Clin Genet 1989; 35: 167–173.Google Scholar
5. Watson, GH: Cardiac rhabdomyomas in tuberous sclerosis. Ann NY Acad Sci 1991; 615: 50–57.Google Scholar
6. Roach, ES, Smith, M, Huttenlocher, P, Bhat, M, Alcorn, D, Hawley, L: Report of the diagnostic criteria committee of the National Tuberous Sclerosis Association. J Child Neurol 1992; 7: 221–224.Google Scholar
7. Sampson, JR, Scahill, SJ, Stephenson, JBP, Mann, L, Connor, JM: Genetic aspects of tuberous sclerosis in the west of Scotland. J Med Genet 1989; 26: 28–31.Google Scholar
8. Janssen, B: Locus Heterogeneity and the Molecular Basis of Tuberous Sclerosis; thesis Erasmus University, Rotterdam, 1995.Google Scholar
9. Connor, JM, Yates, JRW, Mann, L, Aitken, DA, Stephenson, JBP: Tuberous sclerosis: Analysis of linkage to red cell and plasma protein markers. Cytogenet Cell Genet 1987; 44: 63–64.CrossRefGoogle ScholarPubMed
10. Fryer, AE, Chalmers, A, Connor, JM, Fraser, I, Povey, S, Yates, AD, Yates, JRW, Osborne, JP: Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1987; i: 659–661.CrossRefGoogle Scholar
11. Northrup, H, Beaudet, AL, O'Brien, WE, Herman, GE, Lewis, RA, Pollack, MS: Linkage of tuberous sclerosis to ABO blood group. Lancet 1987; ii: 804–805.Google Scholar
12. Renwick, JH: Tuberous sclerosis and ABO. Lancet 197; ii: 1096–1097.Google Scholar
13. Janssen, LAJ, Sandkuijl, LA, Merkens, EC, Maat-Kievit, JA, Sampson, JR, Fleury, , Hennekam, RC, Grosveld, GC, Lindhout, D, Halley, DJJ: Genetic heterogeneity in tuberous sclerosis. Genomics 1990; 8: 237–242.Google Scholar
14. Smith, M, Smalley, S, Cantor, R, Pandolfo, M, Gomez, MI, Baumann, R, Flodman, P, Yoshiyama, K, Nakamura, Y, Julier, C, Dumars, K, Haines, J, Trofatter, J, Spence, MA, Weeks, D, Conneally, M: Mapping of a gene determining tuberous sclerosis to human chromosome 11q14-q23. Genomics 1990; 6: 105–114.CrossRefGoogle Scholar
15. Janssen, LAJ, Povey, S, Attwood, J, Sandkuijl, LA, Lindhout, D, Flodman, P, Smith, M, Sampson, JR, Haines, JL, Merkens, EC, Fleury, P, Short, P, Amos, J, Halley, DJJ: A comparative study on genetic heterogeneity in tuberous sclerosis: Evidence for one gene on 9q34 and a second gene on 11q23. Ann NY Acad Sci 1991; 615: 306–315.CrossRefGoogle Scholar
16. Povey, S, Attwood, J, Janssen, LAJ, Burley, M, Smith, M, Flodman, P, Morton, NE, Edwards, JH, Sampson, JR, Yates, JRW, Haines, JL, Amos, J, Short, MP, Sandkuijl, LA, Halley, DJJ, Fryer, AE, Bech-Hansen, T, Mueller, R, Al-Ghazali, L, Super, M, Osborne, J: An attempt to map two genes for tuberous sclerosis using novel two-point methods. Ann NY Acad Sci 1991; 615: 298–305.CrossRefGoogle ScholarPubMed
17. Fahsold, R, Rott, HD, Lorenz, P: A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase locus. Hum Genet 1991; 88: 85–90.Google Scholar
18. Sampson, JR, Janssen, LAJ, Sandkuijl, LA, and the Tuberous Sclerosis Collaborative Group: Linkage investigation of three putative tuberous sclerosis determining loci on chromosomes 9q, 11q and 12q. J Med Genet 1992; 29: 861–866.Google Scholar
19. Kandt, RS, Haines, JL, Smith, M, Northrup, H, Gardner, RJM, Short, MP, Dumars, K, Roach, ES, Steingold, S, Wall, S, Blanton, SH, Flodman, P, Kwiatkowski, DJ, Jewell, A, Weber, JL, Roses, A, Pericak-Vance, MA: Linkage of an important gene for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet 1992; 2: 37–41.Google Scholar
20. Janssen, B, Sampson, J, der Est, Van, Deelen, W, Verhoef, S, Daniles, I, Hesseling, A, Brook-Carter, P, Nellist, M, Lidhout, D, Sandkuijl, L, Halley, D: Refined localization of TSC1 by combined analysis of 9q34 and 16p13 data in 14 tuberous sclerosis families. Hum Genet 1994; 94: 437–440.CrossRefGoogle ScholarPubMed
21. Sampson, JR, Harris, PC: The molecular genetics of tuberous sclerosis. Hum Mol Genet 1994; 3: 1477–1480.Google Scholar
22. Green, AJ, Johnson, PH, Yates, JRW: The tuberous sclerosis gene on chromosome 9q34 acts as a growth suppressor. Hum Mol Genet 1994; 1833–1834.CrossRefGoogle ScholarPubMed
23. Carbonara, C, Longa, L, Grosso, L: 9q34 loss of heterozygosity in a tuberous sclerosis astrocytoma suggests a growth suppressor-like activity also for the TSC1 gene. Hum Mol Genet 1994; 3: 1829–1832.CrossRefGoogle Scholar
24. Van Slegtenhorst, M, Janssen, B, Nellist, M, Ramlakhan, S, Hermans, C, Hesseling, A, Van den Ouweland, A, Kwiatkowski, D, Eussen, B, Sampson, J, De Jong, P, Halley, D: Cosmid contigs from the tuberous sclerosis candidate region on chromosome 9q34. Eur J Hum Genet 1995.Google Scholar
25. Nahmias, J, Hornigold, N, Fitzgibbon, J, Woodward, K, Pilz, A, Griffin, D, Henske, EP, Nakamura, Y, Graw, S, Florian, F, Benham, F, Povey, S, Wolfe, J: Cosmid contigs spanning 9q34 including the TSC1 candidate region. Eur J Hum Genet 1995.Google Scholar
26. Henske, EP, Short, MP, Jozwiak, S, Bovey, CM, Ramlakhan, S, Haines, JL, Kwiatkowski, DJ: Identification of VAV2 on 9q34 and its exclusion as the tuberous sclerosis gene TSC1. Ann Hum Genet 1995; 59: 25–37.CrossRefGoogle ScholarPubMed
27. Church, DM, Banks, LT, Rogers, AC, Graw, SL, Housman, DE, Gusella, JF, Buckler, AJ: Identification of human chromosome 9 specific genes using exon amplification. Hum Mol Genet 1993; 2: 1915–1920.CrossRefGoogle ScholarPubMed
28. The European Chromosome 16 Tuberous Sclerosis Consortium: Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 1993; 75: 1305–1315.Google Scholar
29. The European Polycystic Kidney Disease Consortium: The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16. Cell 1994; 77: 881–894.CrossRefGoogle Scholar
30. Green, AJ, Smith, M, Yates, JRW: Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 1994; 6: 193–196.Google Scholar
31. Korf, BR: NF1 Genetic Analysis Consortium Newsletter 1994; 2 (4).Google Scholar
32. Cawthon, R, Breidenbach, H: Identification of NF1 mutations by a protein truncation assay. Am J Hum Genet 1994; 55: A: 216.Google Scholar
33. Heim, RA, Silverman, LM, Farber, RA, Kam-Morgan, LNW, Luce, MC: Screening for truncated NF1 proteins. Nat Genet 1994; 8: 218–219.Google Scholar
34. Brook-Carter, PT, Peral, B, Ward, CJ, Thompson, P, Hughes, J, Maheshwar, MM, Nellist, M, Gamble, V, Hariis, PC, Sampson, JR: Deletion of TSC2 and PKD1 genes associated with severe infantile polycystic kidney disease, a contiguous gene syndrome. Nat Genet 1994; 8: 328–332.Google Scholar
35. Verhoef, S, Vrtel, R, Van Essen, T, Bakker, L, Sikkens, E, Halley, D, Lindhout, D, Van den Ouweland, A: Somatic mosaicism and clinical variation in tuberous sclerosis. Lancet 1995; 345: 202.Google Scholar
36. Yeung, RS, Xiao, GH, Jin, F, Lee, WC, Testa, JR, Knudson, AG: Predisposition to renal carcinoma in the Eker rat is determined by germ-line mutation of the tuberous sclerosis 2 (TSC2) gene. Proc Nath Acad Sci USA 1994; 91: 11413–11416.Google Scholar
37. Kobayashi, T, Hirayama, Y, Kobayashi, E, Kubo, Y, Hino, O: A germline mutation in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer. Nat Genet 1995; 9: 70–74.Google Scholar
38. Kobayashi, T, Hirayama, Y, Kobayashi, E, Kubo, Y, Hino, O: A germline mutation in the tuberous sclerosis (Tsc2) gene gives rise to the Eker rat model of dominantly inherited cancer. Erratum. Nat Genet 1995; 9: 218.Google Scholar
39. Northrup, H, Kwiatkowski, DJ, Roach, ES, Dobyns, WB, Lewis, RA, Herman, GE, Rodriguez, E, Daiger, SP, Blanton, SH: Evidence for genetic heterogeneity in tuberous sclerosis: One gene locus on chromosome 9 and at least one locus elsewhere. Am J Hum Genet 1992; 51: 709–720.Google Scholar