The reference OMIM entry for this protein is 188055

Thrombophilia due to activated protein c resistance; thph2
Activated protein c resistance
Apc resistance
Thrombophilia due to deficiency of activated protein c cofactor
Proc cofactor deficiency
Pccf deficiency
Thrombophilia v thrombophili

A number sign (#) is used with this entry because of evidence that the disorder is caused by homozygous or compound heterozygous mutation in the gene that encodes factor V (F5; 612309) on chromosome 1q24.

DESCRIPTION

Thrombophilia due to activated protein C resistance is due to a mutation in the F5 gene that renders factor V resistant to cleavage and inactivation by activated protein C (PROC; 612283) and results in a tendency to thrombosis. See also factor V deficiency (227400), an allelic disorder resulting in a hemorrhagic diathesis due to lack of factor V. The most common mutation that causes this disorder is referred to as factor V Leiden (R506Q; 612309.0001), named after the town in the Netherlands where Bertina et al. (1994) discovered the defect. Homozygosity increases the risk of thrombotic complications to a greater extent that heterozygosity. However, heterozygous presence of the mutation may be combined with defects in other genes in the clotting pathway to contribute to the disorder. Expressivity is variable and influenced by environment.

CLINICAL FEATURES

Dahlback et al. (1993) reported a family in which 5 individuals spanning 3 generations had adult-onset thromboembolic disease, most often deep venous thrombosis of the legs, inherited in an autosomal dominant pattern. Laboratory studies of patients' plasma demonstrated a poor anticoagulant response upon the addition of activated protein C (APC; 612283), as measured by the lack of prolongation of clotting time in an activated partial thromboplastin time (aPTT) assay. In addition, 14 of 19 tested family members showed a similar defect in this assay. Known coagulation defects and serum autoantibodies or inhibitors to APC were excluded. Two additional unrelated patients with thrombophilia and inherited poor response to APC were identified using this novel assay. The thromboembolic events occurred during pregnancy or in the postpartum period in the 2 additional families. Dahlback et al. (1993) concluded that these individuals were lacking a previously unrecognized cofactor for APC that was responsible for the subnormal APC effects in the degradation of factors Va and VIIIa (300841). Greengard et al. (1994) reported variability of thrombosis in a family in which 4 sibs were homozygous for the R560Q mutation. The oldest son, who was homozygous, developed deep vein thrombosis (DVT) of the leg after an injury to that extremity at age 18 years. Two weeks later, during treatment with warfarin, he developed a DVT of the other leg. A clip was placed on the inferior vena cava and warfarin therapy was continued for 2 years. He later developed severe bilateral postphlebitic syndrome with chronic leg ulcers. Another son, who was heterozygous, developed a spontaneous DVT of the leg at age 23 years. The youngest son, who was homozygous, had a spontaneous pulmonary embolus confirmed by pulmonary angiography at the age of 16 years. This recurred 1 year later after the discontinuation of warfarin treatment. At the age of 24, he had a DVT of the right leg when he was not receiving warfarin; he was treated for 6 months. Four months after the discontinuation of treatment, he had a recurrent DVT in the right leg. The heterozygous mother developed a DVT of the left leg during her most recent pregnancy at the age of 37. Two daughters, aged 28 and 33 years, who were homozygous for the mutation, and the father, who was heterozygous, had not developed thrombosis. Greengard et al. ( ... More on the omim web site

Subscribe to this protein entry history

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 188055 was added.