Myotonic dystrophy: Molecular windows on a complex etiology

Željka Korade-Mirnics, Paul Babitzke, Eric Hoffman

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy, with an incidence of ~ 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.

Original languageEnglish (US)
Pages (from-to)1363-1368
Number of pages6
JournalNucleic acids research
Issue number6
StatePublished - Mar 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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