Myotonic dystrophy: A disease model of disorders with dynamic mutation

C. Angelini, E. Menegazzo, M. L. Mostacciuolo, M. Gennarelli, G. Novelli, B. D. Piccola

Research output: Contribution to journalArticlepeer-review

Abstract

We correlated the myotonic dystrophy (DM) phenotype with the degree of [CTG](n) expansion in leukocytes and skeletal muscle in our patients. Analyzing our families we found often the anticipation phenomenon and clinical severity in family members correlated with [CTG](n) expansion. We have used a muscular disability scale (MDRS) and divided our series of DM patients in 3 phenotypic classes: minimal DM in old age, juvenile/adult DM and early child-hood DM. The distribution of the [CTG](n) expansions in leukocytes was analysed for each phenotype class and was found to have a log normal curve. Our results can be used to derive a prognostic index for each phenotypic class, although individual variations may be attributed to somatic mosaicism in different tissues, i.e. larger [CTG](n) expansions in skeletal muscle and other stable tissues. The ability of [CTG](n) mutation to alter the accumulation of poly (A) + RNA in trans in muscle tissue suggests that MD may be an example of a dominant negative mutation manifested at the RNA level. The expression of the DM-PK gene has been explored in skeletal muscle tissue: in muscle there is a selective expression at DM-PK gene product in type 1 fibers. We have observed biochemical and histochemical changes consistent with an altered modulatory mechanism of sarcoplasmic reticulum that may result in myotonia and atrophy of type 1 fibers and concurrent 'slow to fast' transformation. While this may explain the muscle alterations much remains to be studied to understand the multisystemic expression of this disorder.

Original languageEnglish
Pages (from-to)61-63
Number of pages3
JournalActa Cardiomiologica
Volume8
Issue number2
Publication statusPublished - 1996

Keywords

  • [CTG](n) repeat phenotype
  • Genotype correlation
  • Myotonic dystrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology

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