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Genetics of Myotonic Dystrophy

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Myotonic Dystrophy

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Abstract

Myotonic dystrophy (dystrophia myotonica, DM) is the commonest form of muscular dystrophy affecting adults. This multisystem disorder typically affects the skeletal muscle and is characterized by weakness, wasting, and myotonia; other systemic involvement includes ocular, cardiac, endocrine, and central nervous system dysfunction. DM is classified into two main subtypes: type 1 (DM1) and type 2 (DM2) based on mutations in the dystrophia myotonica protein kinase (DMPK) gene and CCHC-type zinc-finger cellular nucleic acid-binding protein (CNBP) formerly known as the zinc finger 9 (ZNF9) gene, respectively. The multisystem phenotype of DM1 and DM2 is due to the presence of expanded repeats and the attendant effects. DM1 occurs due to the persistence of harmful effects of untranslated RNA transcripts of CTG trinucleotide repeat, which are located in the 3′-untranslated region of the DMPK gene on 19q13. DM2 results from the toxic effects of the untranslated RNA transcripts of CCTG tetranucleotide repeat, which are located in the primary intron of the CNBP gene, on chromosome 3q 21.3. A diagnosis of myotonic dystrophy can be made clinically based on presentation with characteristic features and a positive family history. However, molecular genetic testing for an expanded CTG repeat in the DMPK gene is the gold standard for definitive diagnosis of DM1. If DM1 testing is negative, testing for the CCTG repeat in the CNBP gene is then considered appropriate to establish a diagnosis of DM2.

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Abbreviations

CNBP:

Cellular nucleic acid-binding protein

DM:

Myotonic dystrophy

DMPK:

Dystrophia myotonica protein kinase

MBNL:

Muscle blind-like

PROMM:

Proximal myotonic myopathy

RNA:

Ribonucleic acid

ZNF9:

Zinc-finger nuclease 9

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Authors and Affiliations

  1. Division of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan

    Tohru Matsuura

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  1. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan

    Masanori P. Takahashi

  2. Department of Neurology, National Hospital Organization Toneyama National Hospital, Osaka, Japan

    Tsuyoshi Matsumura

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Matsuura, T. (2018). Genetics of Myotonic Dystrophy. In: Takahashi, M., Matsumura, T. (eds) Myotonic Dystrophy. Springer, Singapore. https://doi.org/10.1007/978-981-13-0508-5_1

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