A Database of Deficiency-Causing Mutations and Polymorphisms in the Factor V Gene

Abstract number: P1239

Vos HL

A database has been assembled that lists all known mutations and polymorphisms in the Factor V gene and its flanking regions. The database contains >60 mutations that lead to Factor V deficiency, if present in a homozygous or compound heterozygous state. In addition, it lists >650 polymorphisms, here defined as genetic variations that do not have a major impact on the procoagulant function of Factor V. Several of these polymorphisms are nonetheless of clinical significance, such as Factor V Leiden. All relevant clinical data on the deficiency-causing mutations have been assembled in the database, such as residual expression level, heterozygous or homozygous carriership and literature references. All common types of mutations (insertions/deletions, nonsense, missense and splice site mutations) are represented in the Factor V gene. No obvious clustering of the mutations along the length of the gene is present. However, missense mutations are absent from exon 13, which encodes the B-domain that is removed upon activation of Factor V by thrombin. The data on the polymorphisms lists, among others, their effect on the amino acid sequence, the restriction sites affected and their population frequency, if available. As many as 33 polymorphisms have been described that alter the Factor V amino acid sequence, 16 of which are in exons encoding the important A- and C-domains. Some of these might be mistakenly identified as mutations when present in Factor V-deficient patients. Haplotype information is also provided. On the basis of available data, a recombination hot-spot should be present near intron 6 of the Factor V gene. This has significant implications for studies employing the haplotype structure of this gene. The database is presently formatted as a Word-file and is available upon request, but will be made available as an internet-accessible resource to aid the research of the Factor V community.