title: Five novel mutations in the C1 inhibitor gene (C1NH) leading to a premature stop codon in patients with type I hereditary angioedema.
abstract: Hereditary angioedema (HAE) is a disorder characterised by recurrent attacks of localized subcutaneous or submucosal edema. It is inherited in an autosomal dominant fashion and caused by a deficiency of C1 inhibitor (C1 inh, or C1NH). Most patients with HAE have an absolute deficiency of C1 inh (type I HAE) while the rest (15% of kindreds) synthetize a dysfunctional C1 inh protein (type II HAE). In this report a novel use of denaturing gradient gel electrophoresis (DGGE) followed by direct sequencing of the C1 inhibitor gene is presented. Five novel mutations, one nonsense (p.S48X) and four small deletions resulting in frameshifts (g.2264-2265delAG, g.2304delC, g.8493-8494delCC and g.16676-16677delTG) have been identified in the C1 inhibitor gene in five families with type I HAE. All of these mutations lead to premature termination of translation and thus can be considered causative of the C1 inh deficiency. Moreover, two previously described mutations in the reactive center of C1 inh, p.R444C and p.R444H, have been detected in four unrelated patients with type II HAE.
authors.affiliation: Department of Immunogenetics, Research Institute of Child Health, Brno, Czech Republic. tomf@vuzd.cz
authors.forename: Tomás
authors.initials: T
authors.lastname: Freiberger
authors.forename: Lenka
authors.initials: L
authors.lastname: Kolárová
authors.forename: Pavel
authors.initials: P
authors.lastname: Mejstrík
authors.forename: Martina
authors.initials: M
authors.lastname: Vyskocilová
authors.forename: Pavel
authors.initials: P
authors.lastname: Kuklínek
authors.forename: Jirí
authors.initials: J
authors.lastname: Litzman
mesh_terms: D000799:Angioedema / Q000145:classification* / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein