A nonsense mutation-created intraexonic splice site is active in the lymphocytes, but not in the skeletal muscle of a DMD patient (original) (raw)

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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Acknowledgments

We would like to thank Ms. A. Hosoda for her secretarial help. This work was supported by a grant-in-aid for Scientific Research from the Japan Society for the Promotion of Science; Health, and Labour Sciences Research Grants for Research on Psychiatric and Neurological Diseases and Mental Health; a research grant for Nervous and Mental Disorders from the Ministry of Health, Labour, and Welfare; and the Mitsubishi Foundation.

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Authors and Affiliations

1. Department of Pediatrics, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo, Kobe, 6500017, Japan
   Van Khanh Tran, Yasuhiro Takeshima, Zhujun Zhang, Yasuaki Habara, Atsushi Nishiyama, Mariko Yagi & Masafumi Matsuo
2. Department of Pediatrics, Tohoku University School of Medicine, Sendai, 9808574, Japan
   Kazuhiro Haginoya

Authors

1. Van Khanh Tran
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2. Yasuhiro Takeshima
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3. Zhujun Zhang
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4. Yasuaki Habara
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5. Kazuhiro Haginoya
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6. Atsushi Nishiyama
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7. Mariko Yagi
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8. Masafumi Matsuo
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Corresponding author

Correspondence toMasafumi Matsuo.

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Tran, V.K., Takeshima, Y., Zhang, Z. et al. A nonsense mutation-created intraexonic splice site is active in the lymphocytes, but not in the skeletal muscle of a DMD patient.Hum Genet 120, 737–742 (2007). https://doi.org/10.1007/s00439-006-0241-y

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• Received: 18 June 2006
• Accepted: 01 August 2006
• Published: 26 September 2006
• Issue Date: January 2007
• DOI: https://doi.org/10.1007/s00439-006-0241-y

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