Nucleic Acids Research, Vol 26, Issue 6 1363-1368, Copyright © 1998 by Oxford University Press
Z Korade-Mirnics, P Babitzke and E Hoffman
Myotonic dystrophy (DM) is the most common form of adult onset muscular
dystrophy, with an incidence of approximately 1 in 8500 adults. DM is
caused by an expanded number of trinucleotide repeats in the 3'-
untranslated region (UTR) of a cAMP-dependent protein kinase (DM protein
kinase, DMPK). Although a large number of transgenic animals have been
generated with different gene constructions and knock-outs, none of them
faithfully recapitulates the multisystemic and often severe phenotype seen
in human patients. The transgenic data suggest that myotonic dystrophy is
not caused simply by a biochemical deficiency or abnormality in the DM
kinase gene product. Emerging studies suggest that two novel pathogenetic
mechanisms may play a role in the disease: the expanded repeats appear to
cause haploinsufficiency of a neighboring homeobox gene and also abnormal
DMPK RNA appears to have a detrimental effect on RNA homeostasis. The
complex, multisystemic phenotype may reflect an underlying multifaceted
molecular pathophysiology: the facial dysmorphology may be due to pattern
defects caused by haploinsufficiency of the homeobox gene, while the muscle
disease and endocrine abnormalities may be due to both altered RNA
metabolism and deficiency of the cAMP DMPK protein.
REVIEWS
Myotonic dystrophy: molecular windows on a complex etiology
Department of Molecular Genetics and Biochemistry, BSTW1211, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
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