title: Mutation screening of the C1 inhibitor gene among Hungarian patients with hereditary angioedema.
abstract: Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema caused by the deficiency of activated C1 esterase inhibitor protein (C1-INH, type I (C1NH): reduced serum antigen level, type II: reduced activity and normal serum antigen level). The aim of the present study was to determine the disease-causing mutations in the C1INH gene (SERPING1) among Hungarian HAE-patients. The estimated number of affected HAE-families in Hungary is 40-50, out of which 26 families (type I:23, type II:3) managed in a single center were enrolled in the current study. To detect large deletions/insertions, we used Southern-blotting analysis followed by real time PCR based gene dosage analysis. In the absence of large structural changes, we employed direct sequencing covering the whole coding region and splicing sites of the C1INH gene. Large deletions were detected in 4/23 (17.4%) type I families. We found the g.16788C>T (p.Arg444Cys) mutation in each 3, type II HAE-families. In the remaining type I families, 13 previously unreported mutations (g.638G>A, g.2238C>T, g.2534_2535delCT, g.2579_2620del42, g.2533G>A, g.2695G>A, g.2696_2697insT, g.4467C>T, g.14224A>T, g.14107delA, g.16749_;16775dup, g.16810T>A, g.16885C>G) were detected in 16 families affecting primarily exon 3 (6/13) of the C1INH gene. In the 3 remaining families, known mutations were identified affecting primarily exon 8 (2/3).
authors.affiliation: Laboratory of Molecular Genetics, National Medical Center, Institute of Hematology and Immunology, Budapest, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Kalmár
authors.forename: András
authors.initials: A
authors.lastname: Bors
authors.forename: Henriette
authors.initials: H
authors.lastname: Farkas
authors.forename: Szilvia
authors.initials: S
authors.lastname: Vas
authors.forename: Barbara
authors.initials: B
authors.lastname: Fandl
authors.forename: Lilian
authors.initials: L
authors.lastname: Varga
authors.forename: György
authors.initials: G
authors.lastname: Füst
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
mesh_terms: D000799:Angioedema / Q000175:diagnosis / Q000235:genetics*; D015139:Blotting, Southern; D018389:Codon, Nonsense; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D006814:Hungary; D008297:Male; D009154:Mutation; D020125:Mutation, Missense
chemical_list: D018389:Codon, Nonsense; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; D004247:DNA