title: The search for south European cystic fibrosis mutations: identification of two new mutations, four variants, and intronic sequences.
abstract: The major mutation in the cystic fibrosis (CF) gene is a 3-bp deletion (delta F508) in exon 10. About 50% of the CF chromosomes in Southern Europe carry this mutation, while other previously described mutations account for less than 4%. To identify other common mutations in CF patients from the Mediterranean area, we have sequenced, exon by exon, 16 chromosomes that did not show the delta F508 deletion from a selected panel of eight unrelated CF patients. We describe here one missense and one nonsense mutation, and four sequence polymorphisms. We have also found two previously reported mutations in three chromosomes. Overall, these mutations may account for about 20% of CF alleles in the Italian and Spanish populations. No other mutations were detected in 10 out of 16 CF chromosomes after analyzing about 90% of the coding region of the CF gene, and 39 out of 54 intron/exon boundaries. Therefore, about 26% of CF mutations remain to be identified. In addition we provide the intron/exon boundary sequences for exons 4 to 9. These results together with previously reported linkage data suggest that in the Mediterranean populations further mutations may lie in the promoter region, or in intron sequences not yet analyzed.
authors.affiliation: Institute of Biological Sciences, University of Verona, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Gasparini
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: A
authors.initials: A
authors.lastname: Savoia
authors.forename: M
authors.initials: M
authors.lastname: Dognini
authors.forename: N
authors.initials: N
authors.lastname: Morral
authors.forename: A
authors.initials: A
authors.lastname: Gaona
authors.forename: A
authors.initials: A
authors.lastname: Bonizzato
authors.forename: M
authors.initials: M
authors.lastname: Chillon
authors.forename: F
authors.initials: F
authors.lastname: Sangiuolo
authors.forename: G
authors.initials: G
authors.lastname: Novelli
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D003550:Cystic Fibrosis / Q000235:genetics*; D004247:DNA; D004252:DNA Mutational Analysis; D005091:Exons; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007438:Introns; D007558:Italy; D008969:Molecular Sequence Data; D009154:Mutation; D013030:Spain
chemical_list: D004247:DNA