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

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...

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Bibliographic Details
Published in:Blood 2002-04, Vol.99 (8), p.3063-3065
Main Authors: Schrijver, Iris, Koerper, Marion A., Jones, Carol D., Zehnder, James L.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood Transfusion
Exons
Factor V - genetics
Factor V Deficiency - complications
Factor V Deficiency - genetics
Factor V Deficiency - therapy
Family Health
Female
Frameshift Mutation
Hematologic and hematopoietic diseases
Hemorrhage - etiology
Hemorrhage - genetics
Hemorrhage - therapy
Homozygote
Humans
Male
Medical sciences
Mutation
Pedigree
Platelet diseases and coagulopathies
Point Mutation
RNA Splice Sites - genetics
Sequence Deletion
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Summary: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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood.V99.8.3063