title: Hereditary angioedema in Greek families caused by novel and recurrent mutations.
abstract: This study constitutes the first molecular analysis of hereditary angioedema (HAE) in Greece, where 11 patients from three unrelated families with recurrent angioedema attacks and decreased C1 inhibitor antigenic levels were analyzed for SERPING1 mutations. Interestingly, one family displayed a novel SERPING1 alteration, characterized by the substitution of two consecutive nucleotides TC to AA, resulting in a termination codon (F225X). To the best of our knowledge, this is the first report of such a mutation in SERPING1, causing HAE. The second family displayed the nonsense mutation W482X, and the third the missense mutation M1V, already described in the literature. The type of mutation did not predict clearly the disease phenotype, since even members of the same family displayed a variety of the frequency and the severity of angioedema attacks. Our study identified a novel mutagenesis mechanism for HAE pathogenesis, providing additional evidence for the genetic heterogeneity of the disease.
authors.affiliation: Department of Immunology and Histocompatibility, University of Thessaly Medical School, Larissa, Greece. maspel@med.uth.gr
authors.forename: Matthaios
authors.initials: M
authors.lastname: Speletas
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Boukas
authors.forename: Efimia
authors.initials: E
authors.lastname: Papadopoulou-Alataki
authors.forename: Elena
authors.initials: E
authors.lastname: Tsitsami
authors.forename: Anastasios E
authors.initials: AE
authors.lastname: Germenis
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D054179:Angioedemas, Hereditary / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006115:Greece; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human