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: Y Hagiwara, H Nishio, Y Kitoh, Y Takeshima, N Narita, H Wada, M Yokoyama, H Nakamura, M Matsuo
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 54 Issue 1 Pg. 53-61 (Jan 1994) ISSN: 0002-9297 [Print] United States
• PMID: 8279470 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Primers
• Dystrophin
• RNA Precursors
• RNA, Messenger

Topics

• Adult
• Base Sequence
• DNA Primers
• Dystrophin (genetics)
• Exons
• Humans
• Introns
• Male
• Molecular Sequence Data
• Muscular Dystrophies (genetics)
• Point Mutation
• RNA Precursors (genetics)
• RNA Splicing
• RNA, Messenger (genetics)