title: Identification of a C-->T mutation in the reactive-site coding region of the C1-inhibitor gene and its detection by an improved mutation-specific polymerase chain reaction method.
abstract: Mutations in the C1-inhibitor (C1-INH) gene, leading to low functional levels of C1-inhibitor protein, cause hereditary angioedema (HAE). The disease is characterized by episodic edema in a number of organs. Typically, swellings occur in extremities and face, often accompanied by crampy abdominal pain. Laryngeal edema may lead to suffocation. Type II HAE patients have low functional C1-INH values stemming from only one normal allele. Antigenic C1-INH values, however, are normal or increased owing to the presence of a dysfunctional protein from the mutated allele. The mutations are usually found in exon 8 coding for the amino acids near the reactive centre (P1). Previously, no mutations in the C1-INH gene had been published from the Scandinavian countries. In this work, exon 8 of the C1-inhibitor gene was sequenced in members of two different kindreds, from western and northern Norway, who were suffering from HAE type II. A common point mutation was found within the bait region encoding the reactive centre. The codon CGC was converted to TGC at position 17970, corresponding to an Arg-->Cys replacement which reportedly is the second most frequent type II HAE mutation. This information was utilized to develop a mutation-specific polymerase chain reaction (PCR) for the identification of affected family members. The antisense 17-mer primer (5'-AAGACCAGCAGGGTGCA-3') was successfully applied and AmpliTaq Gold was used in the PCR.
authors.affiliation: Department of Anesthesiology, Nordland Central Hospital, Bodø, Norway.
authors.forename: E W
authors.initials: EW
authors.lastname: Nielsen
authors.forename: H
authors.initials: H
authors.lastname: Fure
authors.forename: P
authors.initials: P
authors.lastname: Winge
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
mesh_terms: D000799:Angioedema / Q000235:genetics*; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D012680:Sensitivity and Specificity
chemical_list: D003174:Complement C1 Inactivator Proteins