Different impact of two mutations of a novel compound heterozygous protein C deficiency with late onset thrombosis

Abstract

ABSTRACT. We investigated the alteration of coagulation state in a protein C (PC) deficiency pedigree and the impact of the PC gene mutations. The pedigree of a proband with cerebral hemorrhagic infarction had sixteen members with four generations. The plasma levels of PC activity (PC:A), protein S activity (PS:A), factor V:C and factor VIII:C, and routine coagulation tests were measured. Nine exons of the PC gene (PROC) were sequenced. Plasma PC:A and PC antigen (PC:Ag) of the proband were 26 and 18%, respectively, which was significantly lower than normal ranges. Two heterozygous missense mutations of PC in the proband were identified, T>G at site 6128 (exon 7) and G>C at site 8478 (exon 9) resulting in F139V and D255H, respectively. The family members with F139V (N = 4) or D255H (N = 4) had lower levels of PC:A and PC:Ag than members with wild-type 2970

Pathogenic variants of PROC gene caused type II activity deficiency in a Chinese family

“…Activated PC plays a crucial role in the regulation of coagulation and PC deficiency is often associated with thrombosis. [6] In this study, our results showed a heterozygous mutation of g1015a (v339 → m339) in exon 9 of the PROC gene in an adult male patient with recurrent cerebral thrombosis. Interestingly, the patient's PC level was normal, but his antigen level was low.…”

“…The type of PC deficiency can be affected by other factors in addition to the gene mutation. [6] Our results revealed that g1015a mutation did not affect the PC level but decreased the antigen level. Alhenc-Gelas et al previously demonstrated that about 25% of PC type II mutation carriers do not display a phenotype in accordance with the mutation category.…”

The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

“…The onset age and mode of the late‐onset patients with double mutations were varied. Late‐onset patients with the double mutations of PROC are rarely reported in Caucasians but are increasing in number in Asian countries (Table ). This discrepancy may be due to the high allelic frequency of FV Leiden and FII variant in Caucasians, which hampers the detection of rare double PROC mutations in adult patients.…”

Evaluation of Protein C Gene Polymorphism in Patients with Pulmonary Embolism

“…As an autosomal dominant trait, hereditary PROC deficiency can arise from several distinct mutations in the PROC gene. PROC variants occurring as the result of these genetic changes lead to severe intracellular impairments and ineffective PROC release [10,11] or non-functional PROC release [12]. Clinical definition of PROC deficiency varies because of the increased risk of VTE complication without any apparent reason in young adults [12].…”

“…PROC variants occurring as the result of these genetic changes lead to severe intracellular impairments and ineffective PROC release [10,11] or non-functional PROC release [12]. Clinical definition of PROC deficiency varies because of the increased risk of VTE complication without any apparent reason in young adults [12]. Prevalence of hereditary PROC deficiency was estimated at 0.2-0.5% [13,14].…”