title: Mutations in the human factor XII gene.
abstract: The factor XII gene from 31 unrelated factor XII-deficient patients from Germany, Switzerland, and Austria was screened for mutations at the genomic level. Several novel mutations were detected and their absence 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 (arginine 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 asparagine (D442N; gene bank accession no. U71275). The novel mutation G570R (glycine 570 to arginine; gene bank accession no. U71274) giving rise to a CRM-positive phenotype is located next to Cys571, which forms a vital disulfide bridge. Two mutations are causing reading frame shifts: one single basepair deletion in exon 12 [exon 12: 10590(DelC); gene bank accession no. U71278] and one acceptor splice site mutation [exon 14: 11397(G --> A); gene bank accession no. L43615]. The putative regulatory mutation exon 1:-8 (g --> c) in the upstream region of the gene is associated with an aberrant Taq I restriction site allele in intron B of the gene (gene bank accession no. X80393).
authors.affiliation: Institut fuer Humangenetik der Universitaet Goettingen, Goettingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schloesser
authors.forename: S
authors.initials: S
authors.lastname: Zeerleder
authors.forename: G
authors.initials: G
authors.lastname: Lutze
authors.forename: W M
authors.initials: WM
authors.lastname: Halbmayer
authors.forename: S
authors.initials: S
authors.lastname: Hofferbert
authors.forename: B
authors.initials: B
authors.lastname: Hinney
authors.forename: H
authors.initials: H
authors.lastname: Koestering
authors.forename: B
authors.initials: B
authors.lastname: Lämmle
authors.forename: G
authors.initials: G
authors.lastname: Pindur
authors.forename: K
authors.initials: K
authors.lastname: Thies
authors.forename: M
authors.initials: M
authors.lastname: Köhler
authors.forename: W
authors.initials: W
authors.lastname: Engel
mesh_terms: D000483:Alleles; D005060:Europe; D005174:Factor XII / Q000235:genetics*; D005260:Female; D015894:Genome, Human; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D005174:Factor XII