title: High heterogeneity for cystic fibrosis in Spanish families: 75 mutations account for 90% of chromosomes.
abstract: We have analyzed 640 Spanish cystic fibrosis (CF) families for mutations in the CFTR gene by direct mutation analysis, microsatellite haplotypes, denaturing gradient gel electrophoresis, single-strand conformation analysis and direct sequencing. Seventy-five mutations account for 90.2% of CF chromosomes. Among these we have detected seven novel CFTR mutations, including four missense (G85V, T582R, R851L and F1074L), two nonsense (E692X and Q1281X) and one splice site mutation (711+3A-->T). Three variants, two in intronic regions (406-112A/T and 3850-129T/C) and one in the coding region (741C/T) were also identified. Mutations G85V, T582R, R851L, E692X and Q1281X are severe, with lung and pancreatic involvement; 711+3A-->T could be responsible for a pancreatic sufficiency/insufficiency variable phenotype; and F1074L was associated with a mild phenotype. These data demonstrate the highest molecular heterogeneity reported so far in CF, indicating that a wide mutation screening is necessary to characterize 90% of the Spanish CF alleles.
authors.affiliation: Medical and Molecular Genetics Center-IRO, Hospital Duran i Reynals, Barcelona, Catalonia, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: M D
authors.initials: MD
authors.lastname: Ramos
authors.forename: J
authors.initials: J
authors.lastname: Giménez
authors.forename: S
authors.initials: S
authors.lastname: Larriba
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D003550:Cystic Fibrosis / Q000453:epidemiology / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005091:Exons; D018740:Genetic Heterogeneity; D005838:Genotype; D006801:Humans; D007438:Introns; D019083:Mediterranean Region; D009154:Mutation; D010641:Phenotype; D017354:Point Mutation; D012326:RNA Splicing; D013030:Spain / Q000453:epidemiology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator