MUTATIONS IN THE HUMAN FACTOR-XII GENE

The factor XII gene from 31 unrelated factor XII-deficient patients fr om Germany, Switzerland, and Austria was screened for mutations at the genomic level. Several novel mutations were detected and their absenc e in a control group of 74 healthy unrelated individuals was checked. Most changes are in the serine protease domain affecting the catalytic triad His-393-Asp-442-Ser-544; two missense mutations, R398Q (arginin e 398 to glutamine; gene bank accession no. U71276) and L395M (leucine 395 to methionine; gene bank accession no. U71277), are close to the active site histidine at position 393. Another mutation detected in a cross-reacting material (CRM)-positive female with a history of three abortions affects the active site aspartic acid by changing it to aspa ragine (D442N; gene bank accession no. U71275). The novel mutation G57 0R (glycine 570 to arginine; gene bank accession no. U71274) giving ri se to a CRM-positive phenotype is located next to Cys571, which forms a vital disulfide bridge. Two mutations are causing reading frame shif ts: one single basepair deletion in exon 12 [exon 12: 10590(DelC); gen e bank accession no. U71278] and one acceptor splice site mutation [ex on 14: 11397(G --> A); gene bank accession no. L43615]. The putative r egulatory mutation exon 1:-8 (g --> c) in the upstream region of the g ene is associated with an aberrant Taq I restriction site allele in in tron B of the gene (gene bank accession no. X80393). (C) 1997 by The A merican Society of Hematology.