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 We identified a previously unpublished sequence variation leading to an Arg 485 Lys substitution in three normal subjects and seven protein C- deficient patients.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.

Metabolic and Genetic Risk Factors for Migraine in Children

“…0.129 m trisodium citrate in plastic tubes. Genetic studies of MTHFR C677T, MTHFR A1298C, PRT and FVL mutations were performed as follows: DNA was isolated from peripheral blood using the FASSST DNA extraction kit (Euroclone, Milan, Italy) and amplified in a Hybaid PCR Express to detect mutations, as previously described (23–26).…”

The investigation and management of inherited thrombophilia

“…This influences the thrombophilic phenotype and has important implications for clinical management. For example, an increased risk for venous thrombosis has been reported for the coinheritance of FV Leiden with AT deficiency (Van Boven et al 1996), PC deficiency Gandrille et al 1995;Hallam et al 1995;Brenner et al 1996), PS deficiency (Koeleman et al 1995;Zoller et al 1995;Beauchamp et al 1996), the prothrombin gene G20210 A variant (Makris et al 1997;Ehrenforth et al 1998;Zoller et al 1998), or hereditary homocystinuria (Mandel et al 1996).…”

Resistance to activated protein C caused by the R506Q mutation in the gene for factor V is a common risk factor for venous thrombosis

“…Thus, the FV:Q 506 allele has been found to be an additional genetic risk factor in families with deficiency of protein C [18. [46][47][48], protein S [17. [49][50][51], or antithrombin [52].…”