title: Incidence of activated protein C resistance caused by the ARG 506 GLN mutation in factor V in 113 unrelated symptomatic protein C-deficient patients. The French Network on the behalf of INSERM.
abstract: Because multiple risk factors in one patient may increase the clinical expression of thrombophilia, we assessed the presence in protein C-deficient patients of the factor V Arg 506 Gln mutation responsible for activated protein C resistance. Using a strategy allowing rapid screening of factor V exon 10, we studied 113 patients with protein C deficiency and 104 healthy volunteers. We detected the Arg 506 Gln mutation in 15 patients (14%) and in one healthy subject (1%). We identified a previously unpublished sequence variation leading to an Arg 485 Lys substitution in three normal subjects and seven protein C-deficient patients. A significant difference in the allelic frequency of the Arg 506 Gln factor V mutation was found between protein C-deficient patients heterozygous for an identified protein C mutation (n = 84; allelic frequency, 4.8%) and protein C-deficient patients with no identified mutation in the protein C gene coding regions (n = 25; allelic frequency, 14%). The results demonstrate that a significant subset of thrombophilic patients has multiple genetic risk factors although additional secondary genetic risk factors remain to be identified for the majority of symptomatic protein C-deficient patients.
authors.affiliation: INSERM U.428, UFR des Sciences Pharmaceutiques, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Gandrille
authors.forename: J S
authors.initials: JS
authors.lastname: Greengard
authors.forename: M
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: I
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: J F
authors.initials: JF
authors.lastname: Abgrall
authors.forename: B
authors.initials: B
authors.lastname: Jude
authors.forename: J H
authors.initials: JH
authors.lastname: Griffin
authors.forename: M
authors.initials: M
authors.lastname: Aiach
mesh_terms: D000293:Adolescent; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003062:Codon / Q000235:genetics; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000150:complications* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D017354:Point Mutation; D011486:Protein C / Q000502:physiology*; D012189:Retrospective Studies; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics*
chemical_list: D003062:Codon; D011486:Protein C; D005165:Factor V