Homozygous factor V splice site mutation associated with severe factor V deficiency.

Blood
Iris SchrijverJames L Zehnder

Abstract

We investigated a family whose proband has a severe bleeding disorder and factor V antigenic and functional levels of 8% and less than 1% of control values, respectively. Molecular analysis of the factor V gene revealed a novel homozygous mutation in the last nucleotide of exon 10. 1701G>T causes activation of a cryptic exonic splice site in exon 10, which encodes part of the factor V heavy chain (A2 domain). This leads to the deletion of 35 nucleotides and results in a frameshift with a premature stop codon at amino acid position 498. The G1701 and corresponding Gln509 are conserved in murine, bovine, and porcine factor V and in human factor VIII. Few factor V deficiency mutations have been identified as yet. Several are present in the heterozygous form in combination with factor V Leiden (Arg506Gln). This is the first reported homozygous splice site mutation in a patient with factor V deficiency.

References

Apr 21, 1992·Biochemistry·L D CripeW H Kane
Dec 1, 1990·Molecular and Cellular Biology·M Talerico, S M Berget
Jul 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·R J JennyK G Mann
Jan 1, 1972·The Medical Clinics of North America·R A Seeler
Jan 22, 1982·Nucleic Acids Research·S M Mount
Aug 1, 1997·American Journal of Human Genetics·T A Cooper, W Mattox
May 12, 1998·British Journal of Haematology·J F GuaschR M Bertina
Jan 14, 1999·British Journal of Haematology·M LakP M Mannucci
Jan 13, 2000·Haemophilia : the Official Journal of the World Federation of Hemophilia·N SaloojaI Hann
Jan 1, 1996·Methods in Molecular Medicine·N C Cross

❮ Previous
Next ❯

Citations

Oct 25, 2003·Nucleic Acids Research·Xavier RocaAdrian R Krainer
Apr 17, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·Q-H FuH-L Wang
Sep 27, 2003·Haemophilia : the Official Journal of the World Federation of Hemophilia·Q FuZ Wang
Jul 23, 2003·Journal of Thrombosis and Haemostasis : JTH·R AsseltaM L Tenchini
Jan 18, 2006·Journal of Thrombosis and Haemostasis : JTH·R AsseltaS Duga
Jan 15, 2009·Haemophilia : the Official Journal of the World Federation of Hemophilia·J N Huang, M A Koerper
Aug 10, 2011·Journal of Thrombosis and Haemostasis : JTH·S Duga, R Asselta
Sep 14, 2017·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Shadi TabibianAkbar Dorgalaleh
Jun 29, 2016·British Journal of Haematology·Francesca NuzzoElisabetta Castoldi
Feb 23, 2019·International Journal of Molecular Sciences·Elvezia Maria ParaboschiRosanna Asselta
Dec 15, 2006·Journal of Thrombosis and Haemostasis : JTH·J S CaudillD P Steensma
Mar 27, 2021·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Satish MaharajRajiv Pruthi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.