Haemophilia A and haemophilia B: molecular insights

Abstract

This review focuses on selected areas that should interest both the scientist and the clinician alike: polymorphisms within the factor VIII and factor IX genes, their linkage, and their ethnic variation; a general assessment of mutations within both genes and a detailed inspection of the molecular pathology of certain mutations to illustrate the diverse cause-effect relations that exist; a summary of current knowledge on molecular aspects of inhibitor production; and an introduction to the new areas of factor VIII and factor IX catabolism. An appendix defining various terms encountered in the molecular genetics of the haemophilias is included, together with an appendix providing accession numbers and locus identification links for accessing gene and sequence information in the international nucleic acid databases.

Genotype-Phenotype Interaction Analyses in Hemophilia

“…Less frequent are the insertion/inversion rearrangements with the exception of intron 22 inversion of factor VIII gene in hemophilia A. This is the most common genetic rearrangement demonstrated in severe disease, comprising 40-50% of cases (Bowen, 2002).…”

Violating the Theory of Single Gene-Single Disorder: Inhibitor Development in Hemophilia

“…It maps to the distal end of the X-chromosome (Xq28) and consists of 26 exons that encode a 2,351 amino acid precursor polypeptide arranged into six domains A1-A2-B-A3-C1-C2 [14,15]. Each of these domains contains specific binding sites for various components of the clotting cascade.…”

“…It often occurs in male, while females are carriers of the disease. Hemophilia A (HA) also known as classic hemophilia, is characterized by a lack of clotting factor VIII and accounts for about 90 % of hemophilia cases; while Hemophilia B (HB) characterized by a lack of clotting factor IX is found to be very rare [1,2]. An estimated worldwide frequency of HA is one per 5,000-7,000 male birth and HB is one per 25,000 male births [3].…”

Combined analysis of the MspI and XbaI polymorphisms in intron 22 of the factor VIII gene for detection of hemophilia A in a Korean population

“…The disorder is caused by mutations in the factor VIII gene (Gitschier et al, 1984;Bowen, 2002). The factor VIII gene is located toward the end of the long arm of the X-chromosome (Xq28) and, at 180 kb and containing 26 exons, is an extremely large gene (Gitschier et al, 1984).…”