title: Detection of C1 inhibitor (SERPING1/C1NH) mutations in exon 8 in patients with hereditary angioedema: evidence for 10 novel mutations.
abstract: Hereditary angioedema (HAE) is caused by mutations in the C1 inhibitor gene (SERPING1, C1NH) and the result is C1 inhibitor deficiency, either in levels or function. We have searched exon 8 for mutations by direct sequencing and analyzed the rest of the exons by SSCP in 87 Spanish families affected by HAE. Out of 87 screened families, we have detected exon 8 mutations in 26. Among these, 17 different mutations were identified: 14 point mutations and 3 frameshift. Seven of the point mutations and the three frameshift were not previously reported. Mutations were: S438P; R444P; V451G; W460X; V468D; G471E; X479R; S417fsX427; I440fsX450; E429fsX450. The rest of the families presented previously reported mutations, 5 missense and two nonsense. In none of the 26 families was an additional change identified in the rest of the exons by SSCP, and, in 20 out of the 22 families with point mutation, we verified that the mutation did not affect a healthy relative. Seven of these families had no history of the disease, and in five of them we were able to verify that the progenitors did not have the mutation. Therefore, they were de novo mutations.
authors.affiliation: Unidad de Inmunología, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046 Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Blanch
authors.forename: Olga
authors.initials: O
authors.lastname: Roche
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Granados
authors.forename: Gumersindo
authors.initials: G
authors.lastname: Fontán
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
mesh_terms: D000799:Angioedema / Q000235:genetics*; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D005091:Exons; D016368:Frameshift Mutation; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015843:Serpins / Q000235:genetics*
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D015843:Serpins