Myotonic dystrophy: emerging mechanisms for DM1 and DM2 - PubMed

Affiliations

• PMID: 16876389
• DOI: 10.1016/j.bbadis.2006.05.013

Free article

Review

Myotonic dystrophy: emerging mechanisms for DM1 and DM2

Diane H Cho et al. Biochim Biophys Acta. 2007 Feb.

Free article

Abstract

Myotonic dystrophy (DM) is a complex multisystemic disorder linked to two different genetic loci. Myotonic dystrophy type 1 (DM1) is caused by an expansion of a CTG repeat located in the 3' untranslated region (UTR) of DMPK (myotonic dystrophy protein kinase) on chromosome 19q13.3. Myotonic dystrophy type 2 (DM2) is caused by an unstable CCTG repeat in intron 1 of ZNF9 (zinc finger protein 9) on chromosome 3q21. Therefore, both DM1 and DM2 are caused by a repeat expansion in a region transcribed into RNA but not translated into protein. The discovery that these two distinct mutations cause largely similar clinical syndromes put emphasis on the molecular properties they have in common, namely, RNA transcripts containing expanded, non-translated repeats. The mutant RNA transcripts of DM1 and DM2 aberrantly affect the splicing of the same target RNAs, such as chloride channel 1 (ClC-1) and insulin receptor (INSR), resulting in their shared myotonia and insulin resistance. Whether the entire disease pathology of DM1 and DM2 is caused by interference in RNA processing remains to be seen. This review focuses on the molecular significance of the similarities and differences between DM1 and DM2 in understanding the disease pathology of myotonic dystrophy.

Similar articles

• Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect.

  Bachinski LL, Udd B, Meola G, Sansone V, Bassez G, Eymard B, Thornton CA, Moxley RT, Harper PS, Rogers MT, Jurkat-Rott K, Lehmann-Horn F, Wieser T, Gamez J, Navarro C, Bottani A, Kohler A, Shriver MD, Sallinen R, Wessman M, Zhang S, Wright FA, Krahe R. Bachinski LL, et al. Am J Hum Genet. 2003 Oct;73(4):835-48. doi: 10.1086/378566. Epub 2003 Sep 10. Am J Hum Genet. 2003. PMID: 12970845 Free PMC article.

• Myotonic dystrophy type 2 and related myotonic disorders.

  Meola G, Moxley RT 3rd. Meola G, et al. J Neurol. 2004 Oct;251(10):1173-82. doi: 10.1007/s00415-004-0590-1. J Neurol. 2004. PMID: 15503094 Review.

• Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9.

  Liquori CL, Ricker K, Moseley ML, Jacobsen JF, Kress W, Naylor SL, Day JW, Ranum LP. Liquori CL, et al. Science. 2001 Aug 3;293(5531):864-7. doi: 10.1126/science.1062125. Science. 2001. PMID: 11486088

• RNA pathogenesis of the myotonic dystrophies.

  Day JW, Ranum LP. Day JW, et al. Neuromuscul Disord. 2005 Jan;15(1):5-16. doi: 10.1016/j.nmd.2004.09.012. Epub 2004 Nov 26. Neuromuscul Disord. 2005. PMID: 15639115 Review.

• Characterization of a single nucleotide polymorphism in the ZNF9 gene and analysis of association with myotonic dystrophy type II (DM2) in the Italian population.

  Vallo L, Bonifazi E, Borgiani P, Novelli G, Botta A. Vallo L, et al. Mol Cell Probes. 2005 Feb;19(1):71-4. doi: 10.1016/j.mcp.2004.09.003. Epub 2004 Nov 12. Mol Cell Probes. 2005. PMID: 15652222

Cited by

• MBNL1 binds GC motifs embedded in pyrimidines to regulate alternative splicing.

  Goers ES, Purcell J, Voelker RB, Gates DP, Berglund JA. Goers ES, et al. Nucleic Acids Res. 2010 Apr;38(7):2467-84. doi: 10.1093/nar/gkp1209. Epub 2010 Jan 13. Nucleic Acids Res. 2010. PMID: 20071745 Free PMC article.

• The reproductive outcome of female patients with myotonic dystrophy type 1 (DM1) undergoing PGD is not affected by the size of the expanded CTG repeat tract.

  Verpoest W, Seneca S, De Rademaeker M, Sermon K, De Rycke M, De Vos M, Haentjens P, Devroey P, Liebaers I. Verpoest W, et al. J Assist Reprod Genet. 2010 Jun;27(6):327-33. doi: 10.1007/s10815-010-9392-9. Epub 2010 Mar 11. J Assist Reprod Genet. 2010. PMID: 20221684 Free PMC article.

• High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2 patients from Finland and Germany.

  Suominen T, Schoser B, Raheem O, Auvinen S, Walter M, Krahe R, Lochmüller H, Kress W, Udd B. Suominen T, et al. J Neurol. 2008 Nov;255(11):1731-6. doi: 10.1007/s00415-008-0010-z. Epub 2008 Sep 24. J Neurol. 2008. PMID: 18807109 Free PMC article.

• Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca²⁺ signal in myotonic dystrophy type 1 myotubes.

  Santoro M, Piacentini R, Perna A, Pisano E, Severino A, Modoni A, Grassi C, Silvestri G. Santoro M, et al. Neural Regen Res. 2020 Sep;15(9):1757-1766. doi: 10.4103/1673-5374.276336. Neural Regen Res. 2020. PMID: 32209783 Free PMC article.

• Biological Efficacy and Toxicity of Diamidines in Myotonic Dystrophy Type 1 Models.

  Siboni RB, Bodner MJ, Khalifa MM, Docter AG, Choi JY, Nakamori M, Haley MM, Berglund JA. Siboni RB, et al. J Med Chem. 2015 Aug 13;58(15):5770-80. doi: 10.1021/acs.jmedchem.5b00356. Epub 2015 Jul 21. J Med Chem. 2015. PMID: 26103061 Free PMC article.

Publication types

MeSH terms

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information

• Miscellaneous

  • NCI CPTAC Assay Portal