Invited Reviews
Clinical and molecular aspects of the myotonic dystrophies: A review
Laura Machuca-Tzili MD,
David Brook PhD,
David Hilton-Jones MD,
Laura Machuca-Tzili MD
Department of Genetics, University of Nottingham, Nottingham, United Kingdom
Search for more papers by this authorDavid Brook PhD
Department of Genetics, University of Nottingham, Nottingham, United Kingdom
Search for more papers by this authorCorresponding Author
David Hilton-Jones MD
Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United KingdomSearch for more papers by this authorLaura Machuca-Tzili MD,
David Brook PhD,
David Hilton-Jones MD,
Laura Machuca-Tzili MD
Department of Genetics, University of Nottingham, Nottingham, United Kingdom
Search for more papers by this authorDavid Brook PhD
Department of Genetics, University of Nottingham, Nottingham, United Kingdom
Search for more papers by this authorCorresponding Author
David Hilton-Jones MD
Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United Kingdom
Department of Clinical Neurology, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, United KingdomSearch for more papers by this authorAbstract
Type 1 myotonic dystrophy or DM1 (Steinert's disease), which is the commonest muscular dystrophy in adults, has intrigued physicians for over a century. Unusual features, compared with other dystrophies, include myotonia, anticipation, and involvement of other organs, notably the brain, eyes, smooth muscle, cardiac conduction apparatus, and endocrine system. Morbidity is high, with a substantial mortality relating to cardiorespiratory dysfunction. More recently a second form of multisystem myotonic disorder has been recognized and variously designated as proximal myotonic myopathy (PROMM), proximal myotonic dystrophy (PDM), or DM2. For both DM1 and DM2 the molecular basis is expansion of an unstable repeat sequence in a noncoding part of a gene (DMPK in DM1 and ZNF9 in DM2). There is accumulating evidence that the basic molecular mechanism is disruption of mRNA metabolism, which has far-reaching effects on many other genes, in part through the induction of aberrant splicing, explaining the multisystemic nature of the disease. The unstable nature of the expansion provides a molecular explanation for anticipation. This review emphasizes the clinical similarities and differences between DM1 and DM2. It examines current views about the molecular basis of these disorders, and contrasts them with other repeat expansion disorders that have increasingly been recognized as a cause of neurological disease. Muscle Nerve, 2005
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