Progression of muscle histopathology but not of spliceopathy in myotonic dystrophy type 2

Rosanna Cardani, Marzia Giagnacovo, Giulia Rossi, Laura V. Renna, Enrico Bugiardini, Chiara Pizzamiglio, Annalisa Botta, Giovanni Meola

Research output: Contribution to journalArticle


Myotonic dystrophy type 2 (DM2) is an autosomal dominant progressive disease involving skeletal and cardiac muscle and brain. It is caused by a tetranucleotide repeat within the first intron of the CNBP gene that leads to an alteration of the alternative splicing of several genes. To understand the molecular mechanisms that play a role in DM2 progression, the evolution of skeletal muscle histopathology and biomolecular findings in successive biopsies have been studied. Biceps brachii biopsies from 5 DM2 patients who underwent two successive biopsies at different years of age have been used. Muscle histopathology has been assessed on sections immunostained with fast or slow myosin. FISH in combination with MBNL1-immunofluorescence has been performed to evaluate ribonuclear inclusion and MBNL1 foci dimensions in myonuclei. Gene and protein expression and alteration of alternative splicing of several genes have been evaluated over time. All DM2 patients examined show a worsening of muscle histopathology and an increase of foci dimensions over time. The progressive worsening of myotonia in DM2 patients may be due to the decrease of CLCN1 mRNA observed in all patients examined. However, a worsening of alternative splicing alterations has not been evidenced over time. The data obtained in this study confirm that DM2 is a slow progression disease since histological and biomolecular alterations observed in skeletal muscle are minimal even after 10-year interval. The data indicate that muscle morphological alterations evolve more rapidly over time than the molecular changes thus indicating that muscle biopsy is a more sensitive tool than biomolecular markers to assess disease progression at muscle level.

Original languageEnglish
Pages (from-to)1042-1053
Number of pages12
JournalNeuromuscular Disorders
Issue number12
Publication statusPublished - Dec 1 2014


  • Alternative splicing
  • Disease progression
  • Muscle histology
  • Myotonic dystrophy type 2
  • Ribonuclear inclusions

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Genetics(clinical)
  • Neurology
  • Medicine(all)

Fingerprint Dive into the research topics of 'Progression of muscle histopathology but not of spliceopathy in myotonic dystrophy type 2'. Together they form a unique fingerprint.

  • Cite this