title: Identification and characterization of three large deletions and a deletion/polymorphism in the CFTR gene.
abstract: Cystic fibrosis (CF) is mainly caused by small molecular lesions of the CFTR gene; mutation detection methods based on conventional PCR do not allow the identification of all CF alleles in a population and large deletions may account for a number of these unidentified molecular lesions. It is only recently that the availability of quantitative PCR methodologies made the search for large gene rearrangements easier in autosomal diseases. Using a combination of different methods, nine of the 37 unidentified CF alleles (24%) were found to harbor large deletions in our cohort of 1600 CF alleles. Three are new deletions, and we report the breakpoints of the previously described EX4_EX10del40kb deletion. An intronic deletion polymorphism affecting intron 17b was also found on almost 1% of "normal" chromosomes. Examination of the breakpoint sequences confirmed that intron 17b is indeed a hot spot for deletions, and that most of these rearrangements are caused by non-homologous recombination.
authors.affiliation: Biochimie Pédiatrique, Hôpital Debrousse, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Chevalier-Porst
authors.forename: G
authors.initials: G
authors.lastname: Souche
authors.forename: D
authors.initials: D
authors.lastname: Bozon
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator