title: A 32-bp deletion (2991del32) in the cystic fibrosis gene associated with CFTR mRNA reduction.
abstract: Cystic fibrosis, a common recessive disorder of exocrine glands, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. We describe the identification of a 32-bp deletion within the coding region of CFTR that involves the nucleotides 2991-3022 in exon 15 (2991del32). This unusual frameshift mutation was confirmed in three unrelated German families, accounting for a frequency of 0.3% in 1,028 CF chromosomes. All identified patients are compound heterozygotes for 2991del32 and for the most frequent cystic fibrosis mutation, delta F508. The evaluation of clinical data revealed typical symptoms of cystic fibrosis, including pancreatic insufficiency, in all three index cases. To characterize further the mutation in the CFTR transcript, we analysed RNA from lymphocytes by reverse transcription and PCR amplification. 2991del32 transcripts were detectable neither in the RNA sample from a patient compound heterozygous delta F508/2991del32 nor in the parental sample heterozygous wild-type/2991del32. These data indicate that the 32-bp deletion causes a pancreas insufficient cystic fibrosis phenotype by a severe reduction of CFTR mRNA.
authors.affiliation: Klinische Forschergruppe Molekulare Pathologie der Mukoviszidose OE 6711, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dörk
authors.forename: K
authors.initials: K
authors.lastname: Will
authors.forename: K
authors.initials: K
authors.lastname: Grade
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: C505032:CFTR protein, human; D017931:DNA Primers; D008565:Membrane Proteins; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA