Abstract
Haemophilia B (Christmas disease) is an inherited, recessive, sex-linked, haemorrhagic condition caused by a defect in the intrinsic clotting factor IX. This disease occurs in males at a frequency of ∼1 in 30,000. Patients differ in the severity of their clinical symptoms, and variation in the clotting activity and in the concentration of factor IX antigen in their plasma has been demonstrated1. There is probably heterogeneity in the molecular defects of the factor IX gene causing the disease. Here we study a severely affected, antigen-negative patient, and show that the only significant sequence difference from the normal factor IX gene is a point mutation changing the obligatory GT to a TT within the donor splice junction of exon f. We infer that this change is the cause of the disease in this individual. In addition, we have used oligodeoxynucleotide probes specific for this mutation to demonstrate the feasibility of carrier detection and prenatal diagnosis for relatives of the patient.
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
McKee, P. A. in The Metabolic Basis of Inherited Disease 5th edn (eds Stanbury et al.) 1531–1560 (McGraw-Hill, New York, 1983).
Anson, D. S. et al. EMBO J. 3, 1053–1060 (1984.
Bertina, R. M. & van der Linden, I. K. in Methods in Hematology Vol. 5 (ed. Bloom, A. L.) 137–155 (Churchill Livingstone, Edinburgh, 1982).
Noyes, C. M., Griffith, M. J., Roberts, H. R. & Lundblad, R. L. Proc. natn. Acad. Sci. U.S.A. 80, 4200–4202 (1983).
Giannelli, F. et al. Nature 303, 181–182 (1983).
Ferrari, N. thesis, Univ. Oxford (1984).
Holmberg, L. et al. Blood 56, 397–401 (1980).
Austen, D. E. G. & Rymes, I. L. A Laboratory Manual of Blood Coagulation. (Blackwell Scientific, Oxford, 1975).
Grosveld, F. et al. Nucleic Acids Res. 10, 6715–6732 (1982).
Maniatis, T., Fritsch, E. F. & Sambrook, J. Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory, New York, 1982).
Murray, N. E., Brammer, W. J. & Murray, K. Molec. gen. Genet. 150, 53–61 (1977).
Grunstein, M. & Hogness, D. S. Proc. natn. Acad. Sci. U.S.A. 72, 3961–3965 (1975).
Maxam, A. M. & Gilbert, W. Meth. Enzym. 65, 499–560 (1980).
Winship, P. R., Anson, D. S., Rizza, C. R. & Brownlee, G. G. Nucleic Acids Res. 12, 8861–8872 (1984).
Matthes, H. W. D. et al. EMBO J. 3, 801–805 (1984).
Connor, B. J. et al. Proc. natn. Acad. Sci. U.S.A. 80, 278–282 (1983).
Weatherall, D. J., Higgs, D. H., Wood, W. G. & Clegg, J. B. Phil. Trans. R. Soc. B307, 247–259 (1984).
Mount, S. M. Nucleic Acids Res. 10, 459–472 (1982).
Giannelli, F. et al. Lancet i, 239–241 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rees, D., Rizza, C. & Brownlee, G. Haemophilia B caused by a point mutation in a donor splice junction of the human factor IX gene. Nature 316, 643–645 (1985). https://doi.org/10.1038/316643a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/316643a0
This article is cited by
-
A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells
Nature Genetics (1993)
-
A Null mutation in the rhodopsin gene causes rod photoreceptor dysfunction and autosomal recessive retinitis pigmentosa
Nature Genetics (1992)
-
Mouse Small eye results from mutations in a paired-like homeobox-containing gene
Nature (1991)
-
A 3′ splice site consensus sequence mutation in the cystic fibrosis gene
Human Genetics (1990)
-
Identification of an altered splice site in Ashkenazi Tay-Sachs disease
Nature (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.
