title: Uniparental inheritance of microsatellite alleles of the cystic fibrosis gene (CFTR): identification of a 50 kilobase deletion.
abstract: More than 250 mutations have been detected in the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, most of which are single point mutations or small deletions or insertions of a few nucleotides. Here we report the first large deletion identified in the CFTR gene, which involves 50 kb in two stretches of DNA: one of 10 kb from exon 4 to exon 7, and another of 40 kb, spanning exons 11 to 18. The deletion has been detected via uniparental inheritance of CFTR microsatellite alleles (IVS17BTA and IVS17BCA) in 3 independent CF families. Clinical status of the 3 CF patients, of which two have the delta F508 mutation as the other CF allele, suggests that this mutation is responsible for a severe clinical phenotype, indistinguishable from homozygous delta F508 patients. The deletion detected here suggests that other large, but less complex molecular defects could also exist in the CFTR gene.
authors.affiliation: Molecular Genetics Department, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Catalunya, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Morral
authors.forename: V
authors.initials: V
authors.lastname: Nunes
authors.forename: T
authors.initials: T
authors.lastname: Casals
authors.forename: N
authors.initials: N
authors.lastname: Cobos
authors.forename: O
authors.initials: O
authors.lastname: Asensio
authors.forename: J
authors.initials: J
authors.lastname: Dapena
authors.forename: X
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004252:DNA Mutational Analysis; D004276:DNA, Satellite / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D005796:Genes; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010290:Parents; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D013030:Spain
chemical_list: C505032:CFTR protein, human; D004276:DNA, Satellite; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator