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Disease-specific genetic diagnostic strategies for muscle diseases unresolved by short-read sequencing

Journal of Human Genetics (2025)Cite this article

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Abstract

In recent years, whole-exome and whole-genome sequencing have been increasingly applied for the genetic diagnosis of muscle diseases. However, standard short-read sequencing often fails to detect pathogenic variants in some inherited muscle diseases, such as Duchenne/Becker muscular dystrophy (DMD/BMD), facioscapulohumeral muscular dystrophy (FSHD), oculopharyngeal muscular dystrophy (OPMD), and oculopharyngodistal myopathy (OPDM). This review outlines the genetic diagnostic approaches for these conditions, with a particular focus on novel analytical approaches for genetic diagnosis.

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Acknowledgements

We thank all the members of the Medical Genome Center at the NCNP for their daily efforts in analyzing the genetic data that formed the basis of this review.

Funding

This study was supported partly by Intramural Research Grant (5-6, 5-5) for Neurological and Psychiatric Disorders of NCNP; Health, Labor, and Welfare Sciences Research Grants (JPMH23FC1014); and JPMH24FC1009 Matsumura Group: “Research for the Dissemination of Standardized Medical Care for Muscular Dystrophy”. Thank you for your attention.

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  1. Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan

    Yoshihiko Saito & Ichizo Nishino

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  1. Yoshihiko Saito
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Correspondence to Yoshihiko Saito.

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Saito, Y., Nishino, I. Disease-specific genetic diagnostic strategies for muscle diseases unresolved by short-read sequencing. J Hum Genet (2025). https://doi.org/10.1038/s10038-025-01391-5

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