High heterogeneity for cystic fibrosis in Spanish families: 75 mutations account for 90% of chromosomes

Hum Genet. 1997 Dec;101(3):365-70. doi: 10.1007/s004390050643.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cystic Fibrosis / epidemiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Exons
  • Genetic Heterogeneity*
  • Genotype
  • Humans
  • Introns
  • Mediterranean Region
  • Mutation*
  • Phenotype
  • Point Mutation
  • RNA Splicing
  • Spain / epidemiology


  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator