Uniparental inheritance of microsatellite alleles of the cystic fibrosis gene (CFTR): identification of a 50 kilobase deletion

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 ΔF508 mutation as the other CF allele, suggests that this mutation is responsible for a severe clinical phenotype, indistinguishable from homozygous ΔF508 patients. The deletion detected here suggests that other large, but less complex molecular defects could also exist in the CFTR gene.