Abstract
Tuberous sclerosis (TSC) is an autosomal dominant condition with characteristic skin lesions, mental handicap, seizures and the development of hamartomas in the brain, heart, kidneys and other organs. Linkage studies have shown locus heterogeneity with a TSC gene mapped to chromosome 9q34 and a second, recently identified on 16p13.3. We have analysed DMA markers in eight hamartomas and one tumour from TSC patients and found allele loss on 16p13.3 in three angiomyolipomas, one cardiac rhabdomyoma, one cortical tuber and one giant cell astrocytoma. We suggest that the TSC gene on 16p13.3 functions like a tumour suppressor gene, in accordance with Knudsen's hypothesis.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Gomez, M.R. Phenotypes of the tuberous sclerosis complex with a revision of diagnostic criteria. Ann. N.Y. Acad. Sci. 615, 1–7 (1991).
Fryer, A.E. et al. Evidence that the gene for tuberous sclerosis is on chromosome 9. Lancet 1, 659–661 (1987).
Burley, M.W. et al. Linkage Studies in Tuberous Sclerosis. Second International Chromosome 9 Workshop (1993). Cytogenet. cell Genet. (in the press).
Smith, M. et al. Mapping of a gene determining tuberous sclerosis to human chromosome 11 q14–11 q23. Genomics 6, 105–114 (1991).
Fahsold, R., Rott, H.D. & Lorenz, P. A third gene locus for tuberous sclerosis is closely linked to the phenylalanine hydroxylase gene locus. Hum. Genet. 88, 85–90 (1991).
Kandt, R.S. et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nature Genet. 2, 37–41 (1992).
Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75, 1–11 (1993).
Legius, E., Marchuk, D.A., Collins, F.S. & GIover, T.W. Somatic deletion of the neurofibromatosis type 1 gene in a neurofibrosarcoma supports a tumour suppressor gene hypothesis. Nature Genet. 3, 122–126 (1993).
Seizinger, B.R. NF1: a prevalent cause of tumorigenesis in human cancers. Nature Genet. 3, 97–98 (1993).
Comings, D.E. Review of Gomez's ‘Tuberous Sclerosis’. Am. J. hum. Genet. 32, 285–286 (1980).
Knudsen, A.G.J. Mutation and cancer: Statistical study of retinoblastoma. Proc. natn. Acad. Sci. U.S.A. 68, 820–823 (1971).
Smith, S.A., Easton, D.F., Evans, D.R.G. & Ponder, B.A.J. Allele losses in the region 17q12–21 in familial breast and ovarian cancer involve the wild type chromosome. Nature Genet. 2, 128–131 (1991).
Neumann, H.P.H. et al. Angiomyolipoma of the kidney and tuberous sclerosis. Am. J. hum. Genet. 51, A104 (1992).
Webb, D.W., Thomas, R.D. & Osborne, J.P. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch. Dis. Childhood 68, 367–370 (1993).
Harding, C.O. & Pagon, R.A. Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma. Am. J. med. Genet. 37, 443–446 (1990).
Alper, J.C. & Holmes, J.B. The incidence and significance of birthmarks in a cohort of 4,641 newborns. Pediatr. Dermatol. 1, 56–68 (1983).
Rocha, G. & Winkelman, R.K. Connective tissue nevus. Arch. Dermatol. 85, 722–729 (1962).
Maniatis, T.M., Fritsch, E.F. & Sambrook, J. Molecular Cloning; A Laboratory Manual (Cold Spring Harbour Press, New York, 1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Green, A., Smith, M. & Yates, J. Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 6, 193–196 (1994). https://doi.org/10.1038/ng0294-193
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0294-193
This article is cited by
-
Tuberous sclerosis complex: new insights into clinical and therapeutic approach
Journal of Nephrology (2019)
-
mTOR signaling in skeletal development and disease
Bone Research (2018)
-
Microbial Antigens Stimulate Metalloprotease-7 Secretion in Human B-Lymphocytes Using mTOR-Dependent and Independent Pathways
Scientific Reports (2017)
-
Tuberous sclerosis complex
Nature Reviews Disease Primers (2016)
-
A case of tuberous sclerosis complex with concomitant primary hyperparathyroidism due to parathyroid adenoma: a case report
World Journal of Surgical Oncology (2015)