HEMOPHILIA A AND B
Defects in the FVIII gene on chromosome Xq28 are the cause of Haemophilia A, a common recessive, X-linked bleeding disorder. The protein encoded by this gene is coagulation factor VIII.
The FVIII gene comprises 26 exons, spanning some 180 kb of genomic DNA (isoform A) on Xq28. Most individuals with FVIII defects have point mutations or inversions in the FVIII gene, most of which will not be detected by the MLPA technique. However, deletions of part or the complete FVIII gene have also been described and these can be detected by MLPA.
The term hemophilia is used in reference to hemophilia A (Factor VIII deficiency); hemophilia B or Christmas disease (factor IX deficiency) and von Willebrand disease (von Willebrand factor deficiency). Hemophilia A and B are both X-linked disorders.
Factor IX Deficiency or Christmas disease (plasma thromboplastic component deficiency) is the result of a hereditary defect in the F9 gene. F9, located on chromosome Xq27.1 and responsible for hemophilia B, is not allelic and consist of two polypeptide chains referred to as the L (light) and H (heavy) chains. Thus, two non-allelic forms of hemophilia B or Factor IX deficiency may exist. Factor IX circulates as an inactive zymogen until proteolytic release of its 'activation peptide' allows it to assume the conformation of an active serine protease. Its role in the blood coagulation cascade is to activate Factor X through interactions with calcium,membrane phospholipids, and Factor VIII. Another procoagulant serine protease activated molecule is Factor VII which also plays an important role in blood clotting. Upon injury, a complex of Factor XII and tissue factor (TF) is formed. This complex triggers the activation of the coagulation cascade through the proteolytic cleavage of both Factor IX and Factor X. Complete absence of Factor VII activity is incompatible with life. Severe bleeding disorder phenotype is only observed in individuals homozygous for mutation in their F7 gene. Hemophilia A is an X-linked, recessive, bleeding disorder caused by a deficiency in the activity of coagulation Factor VIII. Affected individuals develop a variable phenotype of hemorrhage into joints and muscles, easy bruising and prolonged bleeding from wounds. The disorder is caused by heterogeneous mutations in the factor 8 gene which maps to Xq28.
This P207-C1 F9 probemix contains probes for all 8 exons of the F9 gene, spanning ~30 kb of genomic DNA on chromosome Xq27.1. Two probes are present for exon 8. The F7 gene (9 exons) spans ~15kb of genomic DNA and is located on 13q34. For all F7 exons a probe is present except for exon 3, but two probes are included for exon 8. The F8 gene (26 exons), spans ~180 kb of genomic DNA (isoform A) and is located on chromosome Xq28. For the F8 gene 7 probes are included. Finally, 16 reference probes are included in this probemix, detecting several different autosomal chromosomal locations.