We show that a point mutation causing hemophilia B changes the amino acid at position -4 in the propeptide region of factor IX from an arginine to a glutamine, which results in the expression of a stable longer protein with 18 additional amino acids of the N-terminal propeptide region still attached.
Modification of the N-terminus of human factor IX by defective propeptide cleavage or acetylation results in a destabilized calcium-induced conformation: effects on phospholipid binding and activation by factor XIa.
This patient also developed an antibody to factor IX during replacement therapy, which suggests that deletion of the factor IX gene is not necessary for development of the antibody in hemophilia B patients.
In this study, a more comprehensive analysis of the molecular pathology of haemophilia B in Turkey revealed one large deletion and 33 point mutations in the FIX gene of 34 unrelated patients.
Molecular characterization of haemophilia B (HB) at the factor IX gene (F9) is essential to establish diagnosis, confirm genotype-phenotype correlations and to advise in genetic counselling.
Hemophilia B Kashihara is a severe hemorrhagic disorder in which the factor IX antigen is present in normal amounts but factor IX biological activity is markedly reduced.
In the present study, we report the application of polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis to the screening of seven functionally important factor IX gene (FIX) regions (total length 2.66 kb) in 9 unrelated haemophilia B patients of Portuguese or African origin.
DNA sequence analysis of the Factor IX gene from a hemophilia B patient (98% Factor IX antigen; less than 0.01 unit/ml clotting activity) has identified a point mutation in exon II.
Factor IXAlabama is a variant factor IX molecule responsible for a clinically moderate form of hemophilia B. Twenty-five kilobases (kb) of the variant gene, including seven exons coding for the structural protein, were cloned and characterized.
To determine if the factor IX (FIX) germline mutational pattern in AmerIndians differs from the common and putative endogenous pattern, FIX gene mutations were characterized in an initial sample of 10 AmerIndian Peruvian patients with hemophilia B.