title: A novel point mutation (G-1 to T) in a 5' splice donor site of intron 13 of the dystrophin gene results in exon skipping and is responsible for Becker muscular dystrophy.
abstract: The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. We now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with Becker muscular dystrophy. This defect results from a G-to-T transversion at the terminal nucleotide of exon 13, within the 5' splice site of intron 13, and causes complete skipping of exon 13 during processing of dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a truncated dystrophin lacking 40 amino acids from the amino-proximal end of the rod domain. This is the first report of an intraexon point mutation that completely inactivates a 5' splice donor site in dystrophin pre-mRNA. Analysis of the genomic context of the G-1-to-T mutation at the 5' splice site supports the exon-definition model of pre-mRNA splicing and contributes to the understanding of splice-site selection.
authors.affiliation: Department of Pediatrics, Kobe University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: H
authors.initials: H
authors.lastname: Nishio
authors.forename: Y
authors.initials: Y
authors.lastname: Kitoh
authors.forename: Y
authors.initials: Y
authors.lastname: Takeshima
authors.forename: N
authors.initials: N
authors.lastname: Narita
authors.forename: H
authors.initials: H
authors.lastname: Wada
authors.forename: M
authors.initials: M
authors.lastname: Yokoyama
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D016189:Dystrophin / Q000235:genetics*; D005091:Exons; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009136:Muscular Dystrophies / Q000235:genetics*; D017354:Point Mutation; D012322:RNA Precursors / Q000235:genetics; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D017931:DNA Primers; D016189:Dystrophin; D012322:RNA Precursors; D012333:RNA, Messenger