| Functional defect or quantitative deficiency of coagulation factors are involved in congenital bleeding diseases caused by the abnormality of coagulation related proteins. Molecular biology research was performed on a few diseases such as von Willebrand disease, hemophilia A and B, which are more common in population, and more than 1000 gene defects were founded. Gene therapy is being carried on in some of these diseases. Because of the limitation of disease resource, there are a few reports in the world on some rare bleeding diseases caused by coagulation factors deficiency including factor V, factor â…ª, fibrinogen, thrombinogen, and et al. But the researches on these diseases are beginning in our country.Human coagulation factor V (FV) is a single-chain glycoprotein in plasma with a molecular weight of about 330kd. It is produced by megakaryocytes and circulates in blood as an inactive procoagulant cofactor. FVa forms an essential part of the prothrombinase complex that catalyzes the conversion of prothrombin to thrombin by factor Xa in the presence of calcium and a phospholipid membrane. Activated protein C (APC) inactivates FVa through claevage of FVa and FV is required as a cofactor in the APC-mediated inactivation of factor â…§a (Fâ…§a). Thus, coagulation factor V (FV) plays an important role in maintaining the hemostatic balance in both the formation of thrombin in procoagulant pathway as well as in the protein C anticoagulant pathway. Factor V consists of 3 homologous A-type domains and 2 homologous C-type domains connected by a B domain in the following order: A1-A2-B-A3-C1-C2. Removal of the large B domain from inactive FV by thrombin cleavage yields the activated factor V (FVa), which is made up of a heavy chain of approximately 105kd(A1-A2 domains), and a light chain of approximately 74kd(A3-C1-C2 domains). The gene coding for coagulation FV has been mapped to chromosome 1q23 and spans more than 80kb. It consists of 24 introns and 25 exons, and the messenger RNA (mRNA) encodes a 28-amino-acid leader peptide and a 2196-amino-acid mature protein. Roughly, the heavy chain is encoded by exons 1 to 12 and the light chain by exons 14 to 25. The entire B domain is encoded by a single exon, exon13.Inheritary deficiency of factor V (parahemophillia) is a rare autosomal recessive hereditary bleeding disorder with the estimated morbility approximately is one per one million. The phenotypic expression of FV deficiency is variable. Heterozygotes are usually asymptomatic, whereas homozygous or compound heterozygous patients show mild, moderate, or severe bleeding symptoms during their entire life. Easy bruising, epitaxis, hematomas and, in females, menorrhagia are the usual clinical manifestations. The diagnosis of factor V deficiency can be easily made on the basis of the following criteria: a prolonged prothrombin time (PT) and a partial thromboplastin time (PTT) corrected by the addition of adsorbed normal plasma. No other clotting factor deficiency yields such a pattern. A factor V coagulation assay in needed to establish the precise nature of the defect. Both the activity and immunological assay are important. This combination has shown to be of critical importance in the diagnosis of combined defects. Because of low prevalence of FV deficiency with variable phenotypic expression and complex of FV gene, little is known about the molecular basis underlying this disease. Up to date, more than 200 factor V deficiency cases have been reported in the literature, but the molecular basis for factor V deficiency has been established in only about 20 cases. The mutations in patients with factor V deficiency were identified including point mutation, frameshift mutation, deletion and insertion mutation. Most of them are cluster in 13 exon of FV gene, which represents more then 40% of the whole cDNA. von Willebrand disease (vWD), which is caused by the qualitative and quantitative defects of von Willebrand factor(vWF), is one of the most common inherited human bleeding disorders. Approximately 113...
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