By amplification and direct sequencing, 51 single base substitutions were found in the transcribed sequence of the factor IX genes of patients from 50 distinct families with hemophilia B.
However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15%-20% of normal).
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.
As models we selected F9 nonsense mutations with readthrough-favorable features affecting the pre-peptide and pro-peptide regions of coagulation factor IX (FIX), which cause hemophilia B (HB).
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.
One family affected with the hemophilia B Leyden phenotype was found to have a specific single-base mutation (G----A) at nucleotide -6 of the factor IX gene.
We conclude that this method can be advantageously used for diagnosis purposes in a routine laboratory involved in haemophilia B diagnosis and report nine previously undescribed haemophilia B families with their factor IX mutation.
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.
Factor IXTaipei9 is a factor IX variant from a hemophilia B patient with reduced levels of circulating protein molecules (cross-reacting material reduced, CRM).
Two germline retrotransposition mutations of recent origin were observed in 727 independent mutations (0.28%) in the human factor IX gene (F9) of patients with hemophilia B: 1) a 279 bp insertion in exon H originating from an Alu family of short interspersed elements not previously known to be active and, 2) a 463 bp insertion in exon E of a LINE1 element originating in the maternal grandmother.
For this study, determinants of FIX inhibitor development were compared in hemophilia B mice, in which circulating FIX protein is absent (CRM- factor IX knockout (FIXKO) model) or present (CRM+ missense R333Q-hFIX model) modeling multiple potential therapies.
Polymerase chain reaction analysis of DdeI/intron1, XmnI/intron 3 and HhaI/3' flanking region of the gene for factor IX (F9) was investigated in 68 individuals (23 haemophilia patients, 18 obligate carriers, 27 probable carriers) from 23 families of haemophilia B. Linkage disequilibrium analysis was done and haplotypes were generated employing the expectation-maximization algorithm.
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.