Development and Validation of a New Molecular Diagnostic Assay for Detection of Myotonic Dystrophy Type 2

Genet Test Mol Biomarkers. 2015 Dec;19(12):703-9. doi: 10.1089/gtmb.2015.0135. Epub 2015 Oct 27.


Background: Myotonic dystrophy (DM) is the most common adult form of muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia, and multiorgan involvement. Myotonic dystrophy type 2 (DM2) is caused by a [CCTG] expansion in the ZNF9/CNBP gene. The aim of this work was the validation of the new molecular diagnostic test Myotonic Dystrophy type 2 kit-FL.

Results: A cohort of 126 individuals was analyzed. The results show that 126/126 patients were correctly identified using the new molecular assay. In particular, 74 were DM2 positive, 39 were DM2/DM1 negative and 13 DM2 negative/DM1 positive. Approximately 9.5% (7/74) of the DM2-positive samples had a single sizeable expansion and 85% (63/74) showed multiple bands or smears. Comparative fluorescence in situ hybridization (FISH) analyses, on muscle biopsies, revealed that the sensitivity and specificity were very high (>99%). Equivalent analytical performances were obtained using different DNA extraction methods. Among affected individuals 87.5% (28/32) had electrical myotonia, 69% (22/32) proximal weakness, 41% (13/32) cataracts, and about 37.5% (12/32) cardiac conduction defects. FISH analysis and clinical data were used to support the genetic analysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • DNA Repeat Expansion*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myotonic Dystrophy / diagnosis*
  • Myotonic Dystrophy / genetics*
  • Myotonic Dystrophy / pathology
  • Predictive Value of Tests
  • RNA-Binding Proteins / genetics*
  • Reagent Kits, Diagnostic*


  • CNBP protein, human
  • RNA-Binding Proteins
  • Reagent Kits, Diagnostic