Haemophilia B: database of point mutations and short additions and deletions--fourth edition, 1993

The data base below lists known point mutations and short deletions and additions in the factor IX gene, causing the bleeding disorder haemophilia B or Christmas disease (for reviews, see Brownlee 1988, Giannelli 1989, Thompson 1990, Green et al 1991a) These mutations result in a defective'clotting factor IX-a glycoprotein of 415 amino acid residues normally present in plasma and an essential component of the clotting cascade. The disease is an X-linked inherited recessive disorder affecting 1 in about 30,000 males and only very rarely females. The purpose of this database is to update last year's one (Giannelli et al, 1992) by collecting in an accessible, summary form, molecular data on the causative mutations of haemophilia B patients worldwide. It is not intended to replace primary publications although it does contain a significant amount of unpublished work. We have continued our database numbering system (Giannelli et al (1991) giving all patients a unique Patient Identity Number (PIN or ID number). As in previous years, we have included repeat observations of the same mutation, as well as molecularly unique mutations, but in order to keep the main table to a manageable size we have deleted from the table all the repeats of molecular events that were reported more than 5 times. Such events are entered in the table only once but the FIX:C and FIX:Ag entries show the average of the factor IX values associated with these mutations. The comments relevant to each group of mutations are summarised and a full list of references and PIN numbers is given. The central coordinators will keep the data relative to the excluded mutations in a separate file that will be available on request. The factor IX gene lies on the long arm of the X chromosome at Xq27 and its entire sequence of 33 kb is known (Yoshitake et al, 1985). It contains 8 exons (a-h) encoding 6 major domains of factor IX. These are: (1) exon a-a hydrophobic signal peptide which targets the protein for secretion from the hepatocyte into the blood stream. (2) exons b and c-a propeptide and gla domain,-the latter containing 12 y-carboxyglutamyl residues. This post-translational modification is required for the correct folding and calcium binding of factor IX. (3) exon d-a type B, or first epidermal growth factor-like domain, which shows homology to epidermal growth factor (EGF) and, in addition, contains conserved carboxylate residues including a 1-hydroxyaspartate at amino …