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last update : 23-03-2013
Symbol DM2
Location 3q21
Name myotonic dystrophy 2
Other name(s)
  • proximal myotonic myopathy
  • Ricker syndrome
  • Corresponding gene CNBP
    Other symbol(s) PROMM
    Main clinical features
  • proximal myotonia, distal limb weakness, frontal balding, cataract, cardiac arrhythmia, insulin resistance (INSR splicing alteration) without facial akinesia, with ribonuclear inclusions, key feature of the muscle pathology dues to sequestration of muscleblind proteins
  • variable proximal muscle weakness, myotonia, and precocious cataracts, muscle pain and stiffness are prominent presenting features
  • Genetic determination autosomal dominant
    Function/system disorder cardiovascular
    Type disease
    Gene product
    Name zinc finger protein 9 (CCTG expansion in intron1)
    Gene mutationChromosome rearrangementEffectComments
    repeat expansion   abnormal RNA CCTG repeat expansion in intron 1, leading to accumulation in the ribonuclear inclusions without flanking sequence or effects on ZNF9 mRNA processing or protein expression and to DM2 phenotype
    Remark(s) mutant RNA transcripts of DM2 aberrantly affect the splicing of the same target RNAs, such as chloride channel 1 (CLCN1) and insulin receptor (INSR), resulting in their shared myotonia and insulin resistance
  • myogenic program throughout muscle development and tissue regeneration is intact in DM2 (Pelletier 2009)
  • reduction of CNBP RNA-binding activity in DM2 correlates with a decrease of the protein levels in cytoplasm of DM2 muscle cells and the reduction of CNBP is caused by expression of the mutant CCUG repeats (Huichalaf 2009)
  • expanded CCUG repeats that may exhibit toxicity by sequestering the splicing regulator MBNL1, and selective inhibition of MBNL1-CCUG interaction by small molecules are potential therapeutic agents (PMID: 21768123))