title: Molecular analysis of 23 exons of the CFTR gene in Brazilian patients leads to the finding of rare cystic fibrosis mutations.
abstract: To define mutations present in 23 exons and flanking intronic sequences of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in 95 patients from Rio de Janeiro, Brazil, we carried out single-strand conformation polymorphism analysis and automated direct sequencing. Mutation detection was achieved in 45% of the alleles presented, and complete genotyping (two mutated alleles) was accomplished in 34.7% of the patients. Twenty patients (21.1%) were found to carry only one mutation, whereas mutated alleles could not be observed in 42 patients (44.2%). Eleven mutations were found, of which four were characterized as rare mutations: P205S (1.05%), Y1092X (0.53%), S549R (0.53%), and S4X (0.53%). The DF508 mutation in this population sample showed a frequency of 28.42%. The low number of individuals (10 of 95; 10.5%) with compound heterozygous (DF508/non-DF508) genotypes could indicate the presence of another severe mutation leading to the premature death of these individuals. In 4 of the aforementioned 10 individuals with compound heterozygous genotypes, the D-7-2-1-2 (XV2c-KM19-IVS6a-TUB9-M470-T854) haplotype was defined.
authors.affiliation: Laboratório de Genética Humana, Departamento de Genética, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil 4365, Rio de Janeiro 21045-900, Brazil.
authors.forename: Giselda M K
authors.initials: GM
authors.lastname: Cabello
authors.forename: Pedro H
authors.initials: PH
authors.lastname: Cabello
authors.forename: Koko
authors.initials: K
authors.lastname: Otsuki
authors.forename: Maria Emília
authors.initials: ME
authors.lastname: Gombarovits
authors.forename: Juan C
authors.initials: JC
authors.lastname: Llerena
authors.forename: Octavio
authors.initials: O
authors.lastname: Fernandes
mesh_terms: D000483:Alleles; D001938:Brazil; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator