Hemophilias are
bleeding disorders due to deficiency of the
blood coagulation factor VIII (
hemophilia A) or
factor IX (
hemophilia B), resulting from mutation on the gene coding for
factor VIII or
factor IX.
Hemophilia A is more frequent than
hemophilia B and affects 1:10,000 male newborns. The severity and frequency of hemorrhagic episodes is related to residual activity of
factor VIII present in the plasma and relates to the type of mutation associated with the disorder. Cloning of the
factor VIII gene has enabled researchers to better understand the molecular basis of
hemophilia A, accounting to date, for more than 1,000 mutations associated with the disease. This comprehensive knowledge permits an improved comprehension of the genotype-phenotype relation, establishment of clinical policies when mutations related to higher risk of inhibitors development are known, identification of
hemophilia carriers in case of women related to patients, implementation of a program of genetic counseling and discovery of structural-functional relationship between gene-
protein. This article aims to review the molecular basis of
hemophilia A, laboratory techniques used to characterize mutations and clinical implications involved in the molecular diagnosis of
hemophilia A.