Abstract
The fragile X-mental retardation syndrome1 is defined by a moderate to severe mental retardation associated with a cytogenetic marker, a fragile site localized on the long arm of the X chromosome at band Xq 27 (ref. 2). This syndrome has recently been recognized as one of the major causes of genetically determined mental retardation, and as one of the most important X-linked diseases with respect to its frequency (analogous to that of Duchenne muscular dystrophy or of haemophilia A) and severity3–6. In the absence of treatment, genetic screening for this disease would seem particularly important. Prenatal diagnosis is now feasible although difficult7,8 and detection of heterozygous carriers is only possible in ∼50% of cases1,4,9. The recent demonstration of genetic linkage between the glucose 6-phosphate dehydrogenase (G6PD)–colour blindness cluster (at Xq28) and the fragile X locus has suggested that the fragile site is indeed the site of the mutation10. We show here that the fragile X and haemophilia B loci are closely linked, using as genetic marker a polymorphism of the coagulation factor IX gene11. Our study of a large family has demonstrated transmission through a phenotypically normal male, a feature previously described in retrospective analysis of a few other fragile X pedigrees1,6,12,13. Restriction polymorphisms associated with the factor IX gene should be useful for analysing this peculiar aspect of the genetics of the fragile X syndrome, and for genetic screening of the disease.
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
Tariverdian, G. & Weck, B. Hum. Genet. 62, 95–109 (1982).
Brookwell, R. & Turner, G. Hum. Genet. 63, 77 (1983).
Herbst, D. S. & Miller, J. R. Am. J. med. Genet. 7, 461–469 (1980).
Mattei, J. F., Mattei, M. G., Aumeras, C., Auger, M. & Giraud, F. Hum. Genet. 59, 281–289 (1981).
Fishburn, J., Turner, G., Daniel, A. & Brookwell, R. Am. J. med. Genet. 14, 713–724 (1983).
Jacobs, P. A., Mayer, M., Matsuura, J., Rhoads, F. & Yee, S. C. Hum. Genet. 63, 139–148, (1983).
Shapiro, L. R. et al. Lancet i, 99 (1982).
Sutherland, G. R. & Jacky, P. B. Lancet i, 100 (1982).
Sutherland, G. R. Hum. Genet. 53, 23–27 (1979).
Filippi, G. et al. Am. J. med. Genet. 15, 113–119 (1983).
Camerino, G. et al. Proc. natn. Acad. Sci. U.S.A. (in the press).
Nielsen, K. B., Tommerup, N., Poulsen, H. & Mikkelsen, M. Hum. Genet. 59, 23–25 (1981).
Fryns, J. P. & Van Den Berghe, H. Hum. Genet. 61, 262–263 (1982).
Jaye, M. et al. Nucleic Acids Res. 11, 2325–2335 (1983).
Chudley, A. E. et al. Am. J. med. Genet. 14, 699–712 (1983).
Emery, A. E. H. in Methods in Medical Genetics, 63–75 (Churchill-Livingstone, Edinburgh, 1976).
Whittaker, D. L. Copeland, D. L. & Graham, J. B. Am. J. hum. Genet. 14, 149–158 (1962).
Nussbaum, R. L., Crowder, W. E., Nyhan, W. L. & Caskey, T. Proc. natn. Acad. Sci. U.S.A. 80, 4035–4039 (1983).
Webb, G. C., Rogers, J. G., Pitt, D. B., Halliday, J. & Theobald, T. Lancet ii, 1231–1232 (1981).
Little, P. F. R. in Genetic Engineering Vol. 1 (ed. Williamson, R. ) (Academic. New York, 1981).
Wilson, J. T. et al. Proc. natn. Acad. Sci. U.S.A. 79, 3628–3631 (1982).
Conner, B. J. et al. Proc. natn. Acad. Sci. U.S.A. 80, 278–282 (1983).
Kidd, V. J., Wallace, R. B., Itakura, K. & Woo, S. L. C. Nature 304, 230–234 (1983).
Elles, R. G., Williamson, R., Niazi, M., Coleman, D. V. & Horwell, D. New Engl. J. Med. 308, 1433–1435 (1983).
Botstein, D., White, R. L., Scolnick, M. & Davis, R. W. Am. J. hum. Genet. 32, 314–331, (1980).
Murray, J. M. et al. Nature 300, 69–71 (1982).
Davies, K. E. et al. Nucleic Acids Res. 11, 2303–2312 (1983).
Kingston, H. M., Thomas, N. S. T., Pearson, P. L., Sarfarazi, M. & Harper, P. S. J. med. Genet. 20, 255–258 (1983).
Tsevrenis, H., Mandalaki, T., Volkers, W. S. & Khan, P. M. Cytogenet. Cell Genet. 25, 213 (1979).
Migeon, B. R. et al. Proc. natn. Acad. Sci. U.S.A. 78, 5066–5070 (1981).
Persico, M. G., Toniolo, D., Nobile, C., D'Urso, M. & Luzzato, L. Nature 294, 778–780, (1981).
Mattei, M. G., Mattei, J. F., Vidal, I. & Giraud, F. Hum. Genet. 59, 166–169 (1981).
Hanauer, A. et al. Nucleic Acids Res. 11, 3503–3516 (1983).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Camerino, G., Mattei, M., Mattei, J. et al. Close linkage of fragile X-mental retardation syndrome to haemophilia B and transmission through a normal male. Nature 306, 701–704 (1983). https://doi.org/10.1038/306701a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/306701a0
This article is cited by
-
Review: The fragile X syndrome: Isolation of the FMR-1 gene and characterization of the fragile X mutation
Chromosoma (1992)
-
Physical mapping of DXS134 close to the DXS52 locus
Human Genetics (1989)
-
Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome
Human Genetics (1988)
-
Linkage heterogeneity and fragile X
Human Genetics (1988)
-
Multilocus analysis of the fragile X syndrome
Human Genetics (1988)
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.
