Details of Disease

General Information of Disease (ID: DIS5ZWF1)

• Disease Name: Myotonic dystrophy type 2
• Synonyms: dystrophia myotonica 2; myotonic myopathy, proximal; DM2; dystrophia myotonica type 2; myotonic dystrophy 2; PROMM; ricker disease; myotonic dystrophy type 2; proximal myotonic myopathy; proximal myotonic dystrophy; ricker syndrome; myotonic dystrophy caused by mutation in CNBP; CNBP myotonic dystrophy
• Definition: Myotonic dystrophy type 2 (MD2), also known as proximal myotonic myopathy, is a very rare genetic multi-system disorder of late childhood or adult-onset characterized by mild myotonia, muscle weakness, and rarely cardiac conduction disorders.|This term's classification was reviewed in the context of the Strategic Refinement project (2023) and was determined to be excluded from the 'disorder of visual system' (MONDO:0024458) ontology branch (https://orcid.org/0000-0001-9310-0163)
• Disease Hierarchy:
  DISNBEMX: Myotonic dystrophy
  DIS5ZWF1: Myotonic dystrophy type 2
• Disease Identifiers:
  MONDO ID: MONDO_0011266
  MESH ID: D009223
  UMLS CUI: C2931689
  OMIM ID: 602668
  MedGen ID: 419137
  Orphanet ID: 606
  SNOMED CT ID: 715317001

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 14 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
UCP1	TTI12YJ	Limited	Altered Expression	[1]
AQP7	TTNGCRK	moderate	Biomarker	[2]
BPI	TTXCSDR	moderate	Biomarker	[3]
MGAM	TTXWASR	moderate	Biomarker	[4]
MTMR1	TTHDERA	moderate	Altered Expression	[5]
TRPM6	TTV76RD	moderate	Genetic Variation	[6]
CLCN1	TTUYAF3	Strong	Genetic Variation	[7]
DMPK	TTZQTY2	Strong	Biomarker	[8]
IDE	TT2EDHU	Strong	Altered Expression	[9]
INSR	TTCBFJO	Strong	Biomarker	[10]
IAPP	TTHN8EM	Definitive	Genetic Variation	[11]
SCN4A	TT84DRB	Definitive	Biomarker	[12]
SFRP4	TTX8I1Y	Definitive	Altered Expression	[13]
SLC30A8	TTXIGT7	Definitive	Genetic Variation	[14]

This Disease Is Related to 2 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC25A21	DT2UQYR	moderate	Altered Expression	[15]
SLC30A10	DTYBI73	Definitive	Genetic Variation	[14]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
SI	DE5EO4Y	moderate	Biomarker	[4]
FXN	DEXVHDB	Strong	Biomarker	[16]

This Disease Is Related to 18 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
CELF1	OT6JQ5RS	Limited	Altered Expression	[17]
NKX2-5	OTS1SAWM	Limited	Biomarker	[18]
ATXN10	OTKRDUNN	moderate	Biomarker	[19]
BEAN1	OT0WLH27	moderate	Genetic Variation	[20]
EEF2	OTZ7SZ39	moderate	Biomarker	[21]
EIF2S1	OTM0GDTP	moderate	Altered Expression	[22]
EIF2S2	OTXF0B09	moderate	Altered Expression	[22]
EIF2S3	OTARRES9	moderate	Altered Expression	[22]
PGP	OT6QQ7OR	moderate	Genetic Variation	[23]
PPP2R2B	OTSFVC82	moderate	Biomarker	[19]
PRDM16	OT0BGA27	moderate	Altered Expression	[1]
RAD23B	OT0PGOG3	moderate	Altered Expression	[24]
TAC3	OTOJGM38	moderate	Genetic Variation	[25]
TK2	OTS1V4XB	moderate	Genetic Variation	[20]
CCT3	OTL6EOS1	Strong	Biomarker	[26]
MBNL1	OTOV7J85	Strong	Biomarker	[27]
CNBP	OTTGM9NK	Definitive	Autosomal dominant	[28]
DIO2	OTGPNSLH	Definitive	Genetic Variation	[29]

References

• [1] Type 2 diabetes is associated with decreased PGC1 expression in epicardial adipose tissue of patients with coronary artery disease.J Transl Med. 2016 Aug 19;14(1):243. doi: 10.1186/s12967-016-0999-1.
• [2] Decreased adipocyte glucose transporter 4 (GLUT4) and aquaglyceroporin-7 (AQP7) in adults with morbid obesity: possible early markers of metabolic dysfunction.Hormones (Athens). 2019 Sep;18(3):297-306. doi: 10.1007/s42000-019-00130-8. Epub 2019 Oct 7.
• [3] Towards clinical outcome measures in myotonic dystrophy type 2: a systematic review.Curr Opin Neurol. 2018 Oct;31(5):599-609. doi: 10.1097/WCO.0000000000000591.
• [4] Synthesis, in-vitro -glucosidase inhibition, antioxidant, in-vivo antidiabetic and molecular docking studies of pyrrolidine-2,5-dione and thiazolidine-2,4-dione derivatives.Bioorg Chem. 2019 Oct;91:103128. doi: 10.1016/j.bioorg.2019.103128. Epub 2019 Jul 18.
• [5] Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2).Exp Mol Pathol. 2010 Oct;89(2):158-68. doi: 10.1016/j.yexmp.2010.05.007. Epub 2010 Jun 1.
• [6] Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy.Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11324-9. doi: 10.1073/pnas.1113811109. Epub 2012 Jun 25.
• [7] SCN4A mutation as modifying factor of myotonic dystrophy type 2 phenotype.Neuromuscul Disord. 2015 Apr;25(4):301-7. doi: 10.1016/j.nmd.2015.01.006. Epub 2015 Jan 21.
• [8] Myotonic dystrophies: An update on clinical aspects, genetic, pathology, and molecular pathomechanisms.Biochim Biophys Acta. 2015 Apr;1852(4):594-606. doi: 10.1016/j.bbadis.2014.05.019. Epub 2014 May 29.
• [9] Insulin degrading enzyme is up-regulated in pancreatic cells by insulin treatment.Histol Histopathol. 2018 Nov;33(11):1167-1180. doi: 10.14670/HH-11-997. Epub 2018 May 4.
• [10] Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2.Neuromuscul Disord. 2012 Jul;22(7):604-16. doi: 10.1016/j.nmd.2012.03.004. Epub 2012 Apr 19.
• [11] Multiple target of hAmylin on rat primary hippocampal neurons.Neuropharmacology. 2017 Feb;113(Pt A):241-251. doi: 10.1016/j.neuropharm.2016.07.008. Epub 2016 Oct 13.
• [12] SCN4A as modifier gene in patients with myotonic dystrophy type 2.Sci Rep. 2018 Jul 23;8(1):11058. doi: 10.1038/s41598-018-29302-z.
• [13] Circulating miR-103 family as potential biomarkers for type 2 diabetes through targeting CAV-1 and SFRP4.Acta Diabetol. 2020 Mar;57(3):309-322. doi: 10.1007/s00592-019-01430-6. Epub 2019 Oct 3.
• [14] Implications of impaired zinc homeostasis in diabetic cardiomyopathy and nephropathy.Biofactors. 2017 Nov;43(6):770-784. doi: 10.1002/biof.1386. Epub 2017 Aug 27.
• [15] ZNF9 activation of IRES-mediated translation of the human ODC mRNA is decreased in myotonic dystrophy type 2.PLoS One. 2010 Feb 18;5(2):e9301. doi: 10.1371/journal.pone.0009301.
• [16] Non-B DNA conformations formed by long repeating tracts of myotonic dystrophy type 1, myotonic dystrophy type 2, and Friedreich's ataxia genes, not the sequences per se, promote mutagenesis in flanking regions.J Biol Chem. 2006 Aug 25;281(34):24531-43. doi: 10.1074/jbc.M603888200. Epub 2006 Jun 21.
• [17] Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2.PLoS One. 2013 Dec 20;8(12):e83777. doi: 10.1371/journal.pone.0083777. eCollection 2013.
• [18] RNA toxicity in myotonic muscular dystrophy induces NKX2-5 expression.Nat Genet. 2008 Jan;40(1):61-8. doi: 10.1038/ng.2007.28. Epub 2007 Dec 16.
• [19] RNA-mediated neuromuscular disorders.Annu Rev Neurosci. 2006;29:259-77. doi: 10.1146/annurev.neuro.29.051605.113014.
• [20] CAG repeat RNA as an auxiliary toxic agent in polyglutamine disorders.RNA Biol. 2011 Jul-Aug;8(4):565-71. doi: 10.4161/rna.8.4.15397. Epub 2011 Jul 1.
• [21] Reduction of the rate of protein translation in patients with myotonic dystrophy 2.J Neurosci. 2009 Jul 15;29(28):9042-9. doi: 10.1523/JNEUROSCI.1983-09.2009.
• [22] Expression of RNA CCUG repeats dysregulates translation and degradation of proteins in myotonic dystrophy 2 patients.Am J Pathol. 2009 Aug;175(2):748-62. doi: 10.2353/ajpath.2009.090047. Epub 2009 Jul 9.
• [23] Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus.J Neurol Sci. 2012 Apr 15;315(1-2):60-3. doi: 10.1016/j.jns.2011.11.038. Epub 2011 Dec 29.
• [24] Proteome profile in Myotonic Dystrophy type 2 myotubes reveals dysfunction in protein processing and mitochondrial pathways.Neurobiol Dis. 2010 May;38(2):273-80. doi: 10.1016/j.nbd.2010.01.017. Epub 2010 Feb 4.
• [25] High-fat diet and type 2 diabetes induced disruption of the oestrous cycle and alteration of hormonal profiles, but did not affect subpopulations of KNDy neurones in female rats.J Neuroendocrinol. 2018 Nov;30(11):e12651. doi: 10.1111/jne.12651. Epub 2018 Nov 7.
• [26] Unprecedented hydrophobic stabilizations from a reverse wobble TT mispair in DNA minidumbbell.J Biomol Struct Dyn. 2020 Apr;38(7):1946-1953. doi: 10.1080/07391102.2019.1621211. Epub 2019 May 30.
• [27] Small molecules that target the toxic RNA in myotonic dystrophy type 2.ChemMedChem. 2014 Nov;9(11):2455-62. doi: 10.1002/cmdc.201402095. Epub 2014 Jun 17.
• [28] Premutation allele pool in myotonic dystrophy type 2. Neurology. 2009 Feb 10;72(6):490-7. doi: 10.1212/01.wnl.0000333665.01888.33. Epub 2008 Nov 19.
• [29] Association of the type 2 deiodinase Thr92Ala polymorphism with type 2 diabetes: case-control study and meta-analysis.Eur J Endocrinol. 2010 Sep;163(3):427-34. doi: 10.1530/EJE-10-0419. Epub 2010 Jun 21.