title: Homozygous factor V splice site mutation associated with severe factor V deficiency.
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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Schrijver
authors.forename: Marion A
authors.initials: MA
authors.lastname: Koerper
authors.forename: Carol D
authors.initials: CD
authors.lastname: Jones
authors.forename: James L
authors.initials: JL
authors.lastname: Zehnder
mesh_terms: D001803:Blood Transfusion; D005091:Exons; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000150:complications / Q000235:genetics* / Q000628:therapy; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006470:Hemorrhage / Q000209:etiology / Q000235:genetics / Q000628:therapy; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D022821:RNA Splice Sites; D005165:Factor V