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

Teresa Casals, Maria D. Ramos, Javier Giménez Sara Larriba, Virginia Nunes, Xavier P. Estivill

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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 (406-1124/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.

Original languageEnglish
Pages (from-to)365-370
Number of pages6
JournalHuman Genetics
Issue number3
Publication statusPublished - 1997
Externally publishedYes


ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

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