Abstract
Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3–7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3–9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3–9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5′ hot spot of the DMD gene.
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Acknowledgements
This study was supported by an Intramural Research Grant (26-6) for Neurological and Psychiatric Disorders of the National Center of Neurology and Psychiatry (to AN). This study was approved by the institutional ethical committee of the Shinshu University School of Medicine, Japan (approval number 2270).
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Nakamura, A., Fueki, N., Shiba, N. et al. Deletion of exons 3−9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy. J Hum Genet 61, 663–667 (2016). https://doi.org/10.1038/jhg.2016.28
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DOI: https://doi.org/10.1038/jhg.2016.28
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