A nonsense mutation-created intraexonic splice site is active in the lymphocytes,but not in the skeletal muscle of a DMD patient |
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Authors: | Van Khanh Tran Yasuhiro Takeshima Zhujun Zhang Yasuaki Habara Kazuhiro Haginoya Atsushi Nishiyama Mariko Yagi Masafumi Matsuo |
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Institution: | (1) Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo, Kobe 6500017, Japan;(2) Department of Pediatrics, Tohoku University School of Medicine, Sendai 9808574, Japan |
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Abstract: | Production of semi-functional dystrophin mRNA from the dystrophin gene encoding a premature stop codon has been shown to modify
the severe phenotype of Duchenne muscular dystrophy (DMD). In this study, we report the tissue-specific production of semi-functional
dystrophin mRNA via activation of a nonsense mutation-created intraexonic splice acceptor site. In a DMD patient a novel nonsense
mutation was identified in exon 42. In his lymphocytes semi-functional dystrophin mRNA with a 63-nucleotide deletion in exon
42 (dys-63) was found to be produced. In vitro splicing assay using hybrid minigenes disclosed that the mutation-created intraexonic
splice acceptor site was activated. In his skeletal muscle cells, however, only the authentically spliced dystrophin mRNA
was found. This finding identifies the modulation of the splicing of muscle dystrophin mRNA in cases of DMD as a potential
target for therapeutic strategies to generate a milder phenotype for this disease. |
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