title: The skipping of constitutive exons in vivo induced by nonsense mutations.
abstract: Nonsense mutations create a premature signal for the termination of translation of messenger RNA. Such mutations have been observed to cause a severe reduction in the amount of mutant allele transcript or to generate a peptide truncated at the carboxyl end. Analysis of fibrillin transcript from a patient with Marfan syndrome revealed the skipping of a constitutive exon containing a nonsense mutation. Similar results were observed for two nonsense mutations in the gene encoding ornithine delta-aminotransferase from patients with gyrate atrophy. All genomic DNA sequences flanking these exons that are known to influence RNA splicing were unaltered, which suggests that nonsense mutations can alter splice site selection in vivo.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: H C
authors.initials: HC
authors.lastname: Dietz
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: C A
authors.initials: CA
authors.lastname: Francomano
authors.forename: R J
authors.initials: RJ
authors.lastname: Kendzior
authors.forename: R E
authors.initials: RE
authors.lastname: Pyeritz
authors.forename: G R
authors.initials: GR
authors.lastname: Cutting
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics* / Q000302:isolation & purification; D005091:Exons; D005260:Female; D000071837:Fibrillins; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values
chemical_list: D000071837:Fibrillins; D008840:Microfilament Proteins; D009838:Oligodeoxyribonucleotides; D004247:DNA