The Study On Phenotype And Genotype Of Protein C In A Family With Hereditary Protein C Deficiency

Protein C is a vitamin K-dependent glycoprotein produced mainly in liver. Protein C is activated by thrombin bound to thrombomodulin(TM) in the presence of Ca2+. Activated protein C(APC) is an important anticoagulation protein. It can regulate intravascular blood coagulation by proteolyzing both factor Va and factor Villa.Protein C deficiency may lead to system unbalance between blood coagulation and blood anticoagulation. There are two kinds of protein C deficiency: acquired and congenital. Congenital protein C deficiency is a gene disease with clinical expression of recurrent venous thrombosis. It has two kinds of phenotypes: type I and type II.Our study is focus on the phenotype and genotype of a hereditary protein C deficiency family. The propositus was born in Zhengzhou, Henan province. No obvious factors induced his recurrent venous thrombosis. The phenotype assay showed proteinC activity and protein C antigen level decreased parallel (less 50%). This suggested that he is type I inherited PC deficiency exclude from PS, AT III, PAI deficiency and other acquired factors.PCR-SSCP screening showed two new single strand bands of PC exon VII. DNA sequencing revealed one point mutation, 6219G->A leading to Argl69Gln in PC exon VII. This point mutation induced dysfunction protein and affected the function site ofthrombin.By Bsh 12361 restriction endonuclease analysis, we confirmed that other 8 members in this family have the same point mutation.Further study is needed to discuss whether this point mutation is independent factor or still exists cofactor leading to thrombosis.