Abstract
MARFAN syndrome (MFS), one of the most common genetic disorders of connective tissue, is characterized by skeletal, cardiovascular and ocular abnormalities1. The incidence of the disease is about 1 in 20,000, with life expectancy severely reduced because of cardiovascular complications. As the underlying defect is unknown, MFS diagnosis is based solely on clinical criteria. Certain phenotypic features of MFS are also shared by other conditions, which may be genetically distinct entities although part of a clinical continuum. Immunohistochemical studies have implicated fibrillin, a major component of elastin-associated microfibrils2, in MFS aetiology3, 4. Genetic linkage analysis with random probes has independently localized the MFS locus to chromosome 15 (refs 5–7). Here we report that these two experimental approaches converge with the cloning and mapping of the fibrillin gene to chromosome 15ql5–21, and with the establishment of linkage to MFS. We also isolated a second fibrillin gene and mapped it to chromosome 5q23–31. We linked this novel gene to a condition, congenital contractual arachnodactyly, that shares some of the features of MFS1. Thus, the cosegregation of two related genes with two related syndromes implies that fibrillin mutations are likely to be responsible for different MFS phenotypes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pyeritz, R. E. in Principle and Practice of Medical Genetics 2nd edn (eds Emery, E. H. & Rimoin, D. L.) 1047–1063 (Churchill Livingstone, New York, 1990).
Inoué, S. & Leblond, C. P. Am. J. Anat. 176, 121–138 (1986).
Hollister, D. W., Godfrey, M., Sakai, L. Y. & Pyeritz, R. E. New Engl. J. Med. 323, 152–159 (1990).
Godfrey, M. et al. Am. J. hum. Genet 46, 652–660 (1990).
Kainulainen, K., Pulkkinen, L., Savolainen, A., Kaitila, I. & Peltonen, L. New Engl. J. Med. 323, 935–939 (1990).
Dietz, H. C. et al. Genomics 9, 355–361 (1991).
Tsipouras, P., Sarfarazi, M., Devi, A., Weiffenbach, B. & Boxer, M. Proc. natn. Acad. Scl. U.S.A. 88, 4486–4488.
Sakai, L. Y., Keene, D. R. & Engvall, E. J. Cell Biol. 103, 2499–2509 (1986).
Maddox, B. K., Sakai, L. Y., Keene, D. R. & Glanville, R. W. J. biol. Chem. 264, 21382–21385 (1989).
Carpenter, G. & Cohen, S. J. biol. Chem. 265, 7709–7712 (1990).
Walker, B. A., Beighton, P. H. & Murdoch, J. L. Ann. Intern. Med. 71, 349–352 (1969).
Beals, R. K. & Hecht, F. J. Bone Jt Surg. 53, 987–993 (1971).
Lee, B., Vissing, H., Ramirez, F., Rogers, D. & Rimoin, D. Science 244, 978–980 (1989).
Sambrook, J., Fritsch, E. F. & Maniatis, T. Molecular Cloning, A Laboratory Manual 2nd edn (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989).
Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Mattei, M. G. et al. Hum. Genet. 69, 268–271 (1991).
Lee, B., Vitale, E., Superti-Furga, A., Steinmann, B. & Ramirez, F. J. biol. Chem. 266, 5256–5259 (1991).
Ott, J. Am. J. hum. Genet. 26, 588–597 (1974).
Lathrop, G. M., Lalouel, J. M., Junien, C. & Ott, J. Proc. natn. Acad. Sci. U.S.A. 81, 3443–3446 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, B., Godfrey, M., Vitale, E. et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature 352, 330–334 (1991). https://doi.org/10.1038/352330a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/352330a0
This article is cited by
-
Mass spectrometry-based proteomics identify novel serum osteoarthritis biomarkers
Arthritis Research & Therapy (2022)
-
The jam session between muscle stem cells and the extracellular matrix in the tissue microenvironment
npj Regenerative Medicine (2022)
-
A novel intron mutation in FBN-1 gene identified in a pregnant woman with Marfan syndrome
Hereditas (2021)
-
Phenotypes of Cardiovascular Diseases: Current Status and Future Perspectives
Phenomics (2021)
-
The Importance of Genetic Factors in the Management of Spontaneous Pneumothorax
Current Pulmonology Reports (2020)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.