title: Four novel cystic fibrosis mutations in splice junction sequences affecting the CFTR nucleotide binding folds.
abstract: Single cases of the four novel splice site mutations 1525-1 G-->A (intron 9), 3601-2 A-->G (intron 18), 3850-3 T-->G (intron 19), and 4374 + 1 G-->T (intron 23) were detected in the CFTR gene of cystic fibrosis patients of Indo-Iranian, Turkish, Polish, and German descent. The nucleotide substitutions at the +1, -1, and -2 positions all destroy splice sites and lead to severe disease alleles associated with features typical of gastrointestinal and pulmonary cystic fibrosis disease. The 3850-3 T-to-G change was discovered in a very mildly affected 33-year-old delta F508 compound heterozygote, suggesting that the T-to-G transversion at the less conserved -3 position of the acceptor splice site may retain some wildtype function.
authors.affiliation: Klinische Forschergruppe, Molekulare Pathologie der Mukoviszidose, Zentrum Biochemie, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dörk
authors.forename: U
authors.initials: U
authors.lastname: Wulbrand
authors.forename: B
authors.initials: B
authors.lastname: Tümmler
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009711:Nucleotides / Q000378:metabolism; D012326:RNA Splicing
chemical_list: C505032:CFTR protein, human; D008565:Membrane Proteins; D009711:Nucleotides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator