52 kindreds, referred to as haemophilia B-, were characterized by severe deficiency of factor IX coagulant activity (less than 0.01--0.03 u/ml) and unmeasurable IX:Ag (less than 0.12 u/ml): this genetic variant of the disease appears to be related to a complete or marked suppression of factor IX synthesis.
The authors studied the effect of averaging replicated assays of Factor IX coagulation activity and Factor IX antigen on each plasma specimen in improving the ability to detect carriers of hemophilia B.
It is concluded that the quantitative determination of factor IX antigen may be of value in the detection of carriers of both haemophilia B+ and haemophilia B-.
This variant of factor IX has been demonstrated in the plasma of a patient with severe haemophilia B and in the plasmas of a number of possible carriers from the probands' pedigree.
However, there was a discrepancy between the factor IX antigen determined by the neutralization test and the factor IX procoagulant activity in the patients of both hemophilia BM and hemophilia B+.
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.
A better understanding of the interactions between FIX's activators, cofactors, and substrate, FX, has been gained through the study of naturally occurring variants isolated from patients with hemophilia B and genetically engineered recombinant molecules.
Hemophilia B is a useful model for studying the underlying pattern of recent germline mutations in humans because the observed pattern of mutation in factor IX more closely reflects the underlying pattern of mutation than the observed pattern for many other genes.
The likelihood of a missense mutation causing hemophilia B depends on whether the residue is also conserved in the factor IX-related proteases: factor VII, factor X, and protein C. Most of the possible missense mutations in generically conserved residues (i.e., those conserved in factor IX and in all the related proteases) should cause disease.
To define the precise genetic defects of hemophilia B of Chinese origin, we have used the polymerase chain reaction (PCR) combined with direct sequencing to analyze the amplified DNA fragments containing the entire coding regions and their flanking introns of the factor IX gene from 6 affected individuals.
T296----M, a common mutation causing mild hemophilia B in the Amish and others: founder effect, variability in factor IX activity assays, and rapid carrier detection.
These results, in addition to other properties of the endothelium, including large number of cells, accessibility, and direct contact with the circulating blood, suggest that CECs can serve as an efficient drug delivery vehicle producing factor IX in a somatic gene therapy for hemophilia B.
Sixty probable carriers of haemophilia from 25 families were studied by using coagulation phenotype and DNA analysis: 33 with haemophilia A and 27 with haemophilia B. Coagulation phenotype was based on factor VIII/IX assay and DNA analysis on the examination of restriction fragment length polymorphisms (RFLPs) within and closely linked to factor VIII or IX: 3 RFLP for factor VIII and 3 for factor IX.
This study has identified a previously unreported form of hemophilia B in a patient who was a somatic mosaic for a guanine-to-cytosine transversion at nucleotide 31,170 in the factor IX gene.