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.
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.
Hagiwara
Y
Y
Department of Pediatrics, Kobe University School of Medicine, Japan.
Nishio
H
H
Kitoh
Y
Y
Takeshima
Y
Y
Narita
N
N
Wada
H
H
Yokoyama
M
M
Nakamura
H
H
Matsuo
M
M
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
D017931:DNA Primers; D016189:Dystrophin; D012322:RNA Precursors; D012333:RNA, Messenger