John W. Day, MD, PhD

Publication Details

  • RNA pathogenesis of the myotonic dystrophies NEUROMUSCULAR DISORDERS Day, J. W., Ranum, L. P. 2005; 15 (1): 5-16


    Myotonic dystrophy (dystrophia myotonica, DM) is the most common form of muscular dystrophy in adults. The presence of two genetic forms of this complex multisystemic disease (DM1 and DM2) was unrecognized until the genetic cause of DM1 was identified in 1992. The fact that the DM1 mutation is an untranslated CTG expansion led to extended controversy about the molecular pathophysiology of this disease. When the DM2 mutation was identified in 2001 as being a similarly untranslated CCTG expansion, the molecular and clinical parallels between DM1 and DM2 substantiated the role of a novel mechanism in generating the unusual constellation of clinical features seen in these diseases: the repeat expansions expressed at the RNA level alter RNA processing, at least in part by interfering with alternative splicing of other genes. For example, in both DM1 and DM2, altered splicing of chloride channel and insulin receptor transcripts leads to myotonia and insulin resistance, respectively. Although other mechanisms may underlie the differences between DM1 and DM2, the pathogenic effects of the RNA mechanism are now clear, which will facilitate development of appropriate treatments.

    View details for DOI 10.1016/j.nmd.2004.09.012

    View details for Web of Science ID 000226567900002

    View details for PubMedID 15639115

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