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GENATLAS PHENOTYPE

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
	eye
	neuromuscular
Type	disease

Gene product

Name

zinc finger protein 9 (CCTG expansion in intron1)

Mechanism(s)

Gene mutation	Chromosome rearrangement	Effect	Comments

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))