Skip to main content
SpringerLink
Log in

Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2

  • Original Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Aberrant transcription and mRNA processing of multiple genes due to RNA-mediated toxic gain-of-function has been suggested to cause the complex phenotype in myotonic dystrophies type 1 and 2 (DM1 and DM2). However, the molecular basis of muscle weakness and wasting and the different pattern of muscle involvement in DM1 and DM2 are not well understood. We have analyzed the mRNA expression of genes encoding muscle-specific proteins and transcription factors by microarray profiling and studied selected genes for abnormal splicing. A subset of the abnormally regulated genes was further analyzed at the protein level. TNNT3 and LDB3 showed abnormal splicing with significant differences in proportions between DM2 and DM1. The differential abnormal splicing patterns for TNNT3 and LDB3 appeared more pronounced in DM2 relative to DM1 and are among the first molecular differences reported between the two diseases. In addition to these specific differences, the majority of the analyzed genes showed an overall increased expression at the mRNA level. In particular, there was a more global abnormality of all different myosin isoforms in both DM1 and DM2 with increased transcript levels and a differential pattern of protein expression. Atrophic fibers in DM2 patients expressed only the fast myosin isoform, while in DM1 patients they co-expressed fast and slow isoforms. However, there was no increase of total myosin protein levels, suggesting that aberrant protein translation and/or turnover may also be involved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Allen DL, Leinwand LA (2002) Intracellular calcium and myosin isoform transitions. Calcineurin and calcium-calmodulin kinase pathways regulate preferential activation of the IIa myosin heavy chain promoter. J Biol Chem 277(47):45323–45330

    Article  CAS  PubMed  Google Scholar 

  2. Allen DL, Weber JN, Sycuro LK, Leinwand LA (2005) Myocyte enhancer factor-2 and serum response factor binding elements regulate fast myosin heavy chain transcription in vivo. J Biol Chem 280(17):17126–17134

    Article  CAS  PubMed  Google Scholar 

  3. Auvinen S, Suominen T, Hannonen P, Bachinski LL, Krahe R, Udd B (2008) Myotonic dystrophy type 2 found in two of sixty-three persons diagnosed as having fibromyalgia. Arthritis Rheum 58(11):3627–3631

    Article  PubMed  Google Scholar 

  4. Bachinski LL, Udd B, Meola G et al (2003) 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. Am J Hum Genet 73(4):835–8485

    Article  CAS  PubMed  Google Scholar 

  5. Brook JD, McCurrach ME, Harley HG et al (1992) Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell 68(4):799–808

    Article  CAS  PubMed  Google Scholar 

  6. Brotto MA, Biesiadecki BJ, Brotto LS, Nosek TM, Jin JP (2006) Coupled expression of troponin T and troponin I isoforms in single skeletal muscle fibers correlates with contractility. Am J Physiol Cell Physiol 290(2):567–576

    Article  Google Scholar 

  7. Buj-Bello A, Furling D, Tronchere H et al (2002) Muscle-specific alternative splicing of myotubularin-related 1 gene is impaired in DM1 muscle cells. Hum Mol Genet 11(19):2297–2307

    Article  CAS  PubMed  Google Scholar 

  8. Charlet-Berguerand N, Savkur RS, Singh G, Philips AV, Grice EA, Cooper TA (2002) Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Mol Cell 10(1):45–53

    Article  Google Scholar 

  9. Day JW, Ricker K, Jacobsen JF et al (2003) Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum. Neurology 60(4):657–664

    CAS  PubMed  Google Scholar 

  10. Dubowitz V, Sewry CA (2007) Immunohistochemistry. In: muscle biopsy—a practical approach, 3rd edn. Saunders Elsevier, UK, pp 195–245

  11. Ebralidze A, Wang Y, Petkova V, Ebralidse K, Junghans RP (2004) RNA leaching of transcription factors disrupts transcription in myotonic dystrophy. Science 303(5656):383–387

    Article  CAS  PubMed  Google Scholar 

  12. Fardaei M, Rogers MT, Thorpe HM et al (2002) Three proteins, MBNL, MBLL and MBXL, co-localize in vivo with nuclear foci of expanded-repeat transcripts in DM1 and DM2 cells. Hum Mol Genet 11(7):805–814

    Article  CAS  PubMed  Google Scholar 

  13. Faulkner G, Pallavicini A, Formentin E et al (1999) ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol 146(2):465–475

    Article  CAS  PubMed  Google Scholar 

  14. Fu YH, Pizzuti A, Fenwick RG Jr et al (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255(5049):1256–1258

    Article  CAS  PubMed  Google Scholar 

  15. Grifone R, Laclef C, Spitz F et al (2004) Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype. Mol Cell Biol 24(14):6253–6267

    Article  CAS  PubMed  Google Scholar 

  16. Griggs R, Vihola A, Hackman P et al (2007) Zaspopathy in a large classic late-onset distal myopathy family. Brain 130(Pt 6):1477–1484

    Article  CAS  PubMed  Google Scholar 

  17. Haravuori H, Vihola A, Straub V et al (2001) Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Neurology 56(7):869–877

    CAS  PubMed  Google Scholar 

  18. Harper PS (2001) Myotonic dystrophy. Saunders, London

    Google Scholar 

  19. Horton MJ, Brandon CA, Morris TJ, Braun TW, Yaw KM, Sciote JJ (2001) Abundant expression of myosin heavy-chain IIB RNA in a subset of human masseter muscle fibres. Arch Oral Biol 46(11):1039–1050

    Article  CAS  PubMed  Google Scholar 

  20. Huang C, Zhou Q, Liang P et al (2003) Characterization and in vivo functional analysis of splice variants of cypher. J Biol Chem 278(9):7360–7365

    Article  CAS  PubMed  Google Scholar 

  21. Huichalaf C, Schoser B, Schneider-Gold C, Jin B, Sarkar P, Timchenko L (2009) Reduction of the rate of protein translation in patients with myotonic dystrophy 2. J Neurosci 29(28):9042–9049

    Article  CAS  PubMed  Google Scholar 

  22. Jin J, Wang G-L, Salisbury E, Timchenko L, Timchenko NA (2009) GSK3β-cyclin D3-CUGBP1-eIF2 pathway in aging and in myotonic dystrophy. Cell Cycle 8(15):2356–2360

    CAS  PubMed  Google Scholar 

  23. Kanadia RN, Johnstone KA, Mankodi A et al (2003) A muscleblind knockout model for myotonic dystrophy. Science 302(5652):1978–1980

    Article  CAS  PubMed  Google Scholar 

  24. Kimura T, Nakamori M, Lueck JD et al (2005) Altered mRNA splicing of the skeletal muscle ryanodine receptor and sarcoplasmic/endoplasmic reticulum Ca2+-ATPase in myotonic dystrophy type 1. Hum Mol Genet 14(15):2189–2200

    Article  CAS  PubMed  Google Scholar 

  25. Konig S, Beguet A, Bader CR, Bernheim L (2006) The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion. Development 133(16):3107–3114

    Article  CAS  PubMed  Google Scholar 

  26. Krahe R, Bachinski LL, Udd B (2006) Myotonic dystrophy type 2: clinical and genetic aspects. In: Wells RD, Ashizawa T (eds) Genetic instabilities and neurological diseases, 2nd edn. Academic Press, Boston, pp 131–150

    Google Scholar 

  27. Leroy O, Wang J, Maurage CA et al (2006) Brain-specific change in alternative splicing of tau exon 6 in myotonic dystrophy type 1. Biochim Biophys Acta 1762(4):460–467

    CAS  PubMed  Google Scholar 

  28. Lin X, Miller JW, Mankodi A et al (2006) Failure of MBNL1-dependent post-natal splicing transitions in myotonic dystrophy. Hum Mol Genet 15(13):2087–2097

    Article  CAS  PubMed  Google Scholar 

  29. Liquori CL, Ricker K, Moseley ML et al (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 293(5531):864–867

    Article  CAS  PubMed  Google Scholar 

  30. Machuca-Tzili L, Thorpe H, Robinson TE, Sewry C, Brook JD (2006) Flies deficient in muscleblind protein model features of myotonic dystrophy with altered splice forms of Z-band associated transcripts. Hum Genet 120(4):487–499

    Article  CAS  PubMed  Google Scholar 

  31. Mahadevan M, Tsilfidis C, Sabourin L et al (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255(5049):1253–1255

    Article  CAS  PubMed  Google Scholar 

  32. Mahadevan MS, Yadava RS, Yu Q et al (2006) Reversible model of RNA toxicity and cardiac conduction defects in myotonic dystrophy. Nat Genet 38(9):1066–1070

    Article  CAS  PubMed  Google Scholar 

  33. Mankodi A, Logigian E, Callahan L et al (2000) Myotonic dystrophy in transgenic mice expressing an expanded CUG repeat. Science 289(5485):1769–1773

    Article  CAS  PubMed  Google Scholar 

  34. Mankodi A, Takahashi MP, Jiang H et al (2002) Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Mol Cell 100(1):35–44

    Article  Google Scholar 

  35. Mankodi A, Lin X, Blaxall BC, Swanson MS, Thornton CA (2005) Nuclear RNA foci in the heart in myotonic dystrophy. Circ Res 97(11):1152–1155

    Article  CAS  PubMed  Google Scholar 

  36. Maurage CA, Udd B, Ruchoux MM et al (2005) Similar brain tau pathology in DM2/PROMM and DM1/Steinert disease. Neurology 65(10):1636–1638

    Article  CAS  PubMed  Google Scholar 

  37. McKinsey TA, Zhang CL, Olson EN (2002) MEF2: a calcium-dependent regulator of cell division, differentiation and death. Trends Biochem Sci 27(1):40–47

    Article  CAS  PubMed  Google Scholar 

  38. Molkentin JD, Firulli AB, Black BL et al (1996) MEF2B is a potent transactivator expressed in early myogenic lineages. Mol Cell Biol 16(7):3814–3824

    CAS  PubMed  Google Scholar 

  39. Moraes KCM, Wilusz CJ, Wilusz J (2006) CUG-BP binds to RNA substrates and recruits PARN deadenylase. RNA 12:1084–1091

    Article  CAS  PubMed  Google Scholar 

  40. Olive M, Martinez-Matos JA, Pirretas P, Povedano M, Navarro C, Ferrer I (1997) Expression of myogenic regulatory factors (MRFs) in human neuromuscular disorders. Neuropathol Appl Neurobiol 23(6):475–482

    Article  CAS  PubMed  Google Scholar 

  41. Osborne RJ, Thornton CA (2006) RNA-dominant diseases. Hum Mol Genet 15(Spec No 2):R162–R169

    Article  CAS  PubMed  Google Scholar 

  42. Philips AV, Timchenko LT, Cooper TA (1998) Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy. Science 280(5364):737–741

    Article  CAS  PubMed  Google Scholar 

  43. Potthoff MJ, Wu H, Arnold MA et al (2007) Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers. J Clin Investig 117:2459–2467

    Article  CAS  PubMed  Google Scholar 

  44. Ranum LP, Cooper TA (2006) RNA-mediated neuromuscular disorders. Annu Rev Neurosci 29:259–277

    Article  CAS  PubMed  Google Scholar 

  45. Ricker K, Koch MC, Lehmann-Horn F et al (1995) Proximal myotonic myopathy. Clinical features of a multisystemic disorder similar to myotonic dystrophy. Arch Neurol 52(1):25–31

    CAS  PubMed  Google Scholar 

  46. Sallinen R, Vihola A, Bachinski LL et al (2004) New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2). Neuromuscul Disord 14(4):274–283

    Article  CAS  PubMed  Google Scholar 

  47. Salisbury E, Sakai K, Schoser B et al (2008) Ectopic expression of cyclin D3 corrects differentiation of DM1 myoblasts through activation of RNA CUG-binding protein, CUGBP1. Exp Cell Res 314:2266–2278

    Article  CAS  PubMed  Google Scholar 

  48. Salisbury E, Schoser B, Schneider-Gold C et al (2009) Expression of RNA CCUG repeats dysregulates translation and degradation of proteins in myotonic dystrophy 2 patients. Am J Pathol 175(2):748–762

    Article  CAS  PubMed  Google Scholar 

  49. Salvatori S, Furlan S, Fanin M et al (2009) Comparative transcriptional and biochemical studies in muscle of myotonic dystrophies (DM1 and DM2). Neurol Sci 30(3):185–192

    Article  PubMed  Google Scholar 

  50. Savkur RS, Philips AV, Cooper TA (2001) Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Nat Genet 29(1):40–47

    Article  CAS  PubMed  Google Scholar 

  51. Savkur RS, Philips AV, Cooper TA et al (2004) Insulin receptor splicing alteration in myotonic dystrophy type 2. Am J Hum Genet 74(6):1309–1313

    Article  CAS  PubMed  Google Scholar 

  52. Schneider C, Ziegler A, Ricker K et al (2000) Proximal myotonic myopathy: evidence for anticipation in families with linkage to chromosome 3q. Neurology 55(3):383–388

    CAS  PubMed  Google Scholar 

  53. Schoser BG, Schneider-Gold C, Kress W et al (2004) Muscle pathology in 57 patients with myotonic dystrophy type 2. Muscle Nerve 29(2):275–281

    Article  PubMed  Google Scholar 

  54. Selcen D, Engel AG (2005) Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol 57(2):269–276

    Article  CAS  PubMed  Google Scholar 

  55. Stewart AF, Richard CW 3rd, Suzow J et al (1996) Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family. Genomics 37(1):68–76

    Article  CAS  PubMed  Google Scholar 

  56. Taneja KL, McCurrach M, Schalling M, Housman D, Singer RH (1995) Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. J Cell Biol 128(6):995–1002

    Article  CAS  PubMed  Google Scholar 

  57. Timchenko NA, Cai ZJ, Welm AL, Reddy S, Ashizawa T, Timchenko LT (2001) RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1. J Biol Chem 276(11):7820–7826

    Article  CAS  PubMed  Google Scholar 

  58. Timchenko NA, Iakova P, Cai Z-J, Smith JR, Timchenko LT (2001) Molecular basis for impaired muscle differentiation in myotonic dystrophy. Mol Cell Biol 21:6927–6938

    Article  CAS  PubMed  Google Scholar 

  59. Timchenko NA, Patel R, Iakova P, Cai ZJ, Quan L, Timchenko LT (2004) Overexpression of CUG triplet repeat-binding protein, CUGBP1, in mice inhibits myogenesis. J Biol Chem 279(13):13129–13139

    Article  CAS  PubMed  Google Scholar 

  60. Tschirgi ML, Rajapakse I, Chandra M (2006) Functional consequence of mutation in rat cardiac troponin T is affected differently by myosin heavy chain isoforms. J Physiol 574(Pt 1):263–273

    Article  CAS  PubMed  Google Scholar 

  61. Udd B, Krahe R, Wallgren-Pettersson C, Falck B, Kalimo H (1997) Proximal myotonic dystrophy—a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes? Neuromuscul Disord 7(4):217–228

    Article  CAS  PubMed  Google Scholar 

  62. Udd B, Meola G, Krahe R et al (2003) Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies. 3rd workshop, 14–16 February 2003, Naarden, the Netherlands. Neuromuscul Disord 13(7–8):589–596

    Article  CAS  PubMed  Google Scholar 

  63. Udd B, Meola G, Krahe R et al (2006) 140th ENMC international workshop: myotonic dystrophy DM2/PROMM and other myotonic dystrophies with guidelines on management. Neuromuscul Disord 16(6):403–413

    Article  CAS  PubMed  Google Scholar 

  64. Vatta M, Mohapatra B, Jimenez S et al (2003) Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction. J Am Coll Cardiol 42(11):2014–2027

    Article  CAS  PubMed  Google Scholar 

  65. Vihola A, Bassez G, Meola G et al (2003) Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. Neurology 60(11):1854–1857

    CAS  PubMed  Google Scholar 

  66. Vlasova IA, Tahoe NM, Fan D et al (2008) Conserved GU-rich elements mediate RNA decay by binding to CUG-binding protein 1. Mol Cell 29:263–270

    Article  CAS  PubMed  Google Scholar 

  67. Webster C, Silberstein L, Hays AP, Blau HM (1988) Fast muscle fibers are preferentially affected in duchenne muscular dystrophy. Cell 52(4):503–513

    Article  CAS  PubMed  Google Scholar 

  68. Weiss A, Schiaffino S, Leinwand LA (1999) Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: implications for functional diversity. J Mol Biol 290(1):61–75

    Article  CAS  PubMed  Google Scholar 

  69. Winter A, Bornemann A (1999) NCAM, vimentin and neonatal myosin heavy chain expression in human muscle diseases. Neuropathol Appl Neurobiol 25(5):417–424

    Article  CAS  PubMed  Google Scholar 

  70. Wu QL, Jha PK, Raychowdhury MK, Du Y, Leavis PC, Sarkar S (1994) Isolation and characterization of human fast skeletal beta troponin T cDNA: comparative sequence analysis of isoforms and insight into the evolution of members of a multigene family. DNA Cell Biol 13(3):217–233

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to the participating patients for their cooperation. This study has been accomplished through the active collaboration and sharing of patient samples within the European Neuromuscular Centre (ENMC) consortium on DM2 and Other Myotonic Dystrophies by the following members: Josep Gamez, Jerry Mendell, Guillaume Bassez, Bruno Eymard, Tetsuo Ashizawa, and Lubov Timchenko. We thank Valerie L. Neubauer and Tamara J. Nixon for expert assistance with the generation of microarray expression data, and Georgine Faulkner, Trieste, Italy for the ZASP antibody. The mAb clone A4.74 developed by Helen M. Blau was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA. RK was supported by grants from the National Institutes of Health, NIH (AR48171), Muscular Dystrophy Association USA and the Kleberg Foundation. BU was supported by funding from the Folkhälsan Research Foundation, and grants from the Liv & Hälsa Foundation, the Vasa Central Hospital District Medical Research funds and Kung Gustav V Adolfs och Drottning Victorias minnesfond Foundation.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Folkhälsan Institute of Genetics, University of Helsinki, 00014, Helsinki, Finland

    Anna Vihola, Jeanette Holmlund-Hampf & Bjarne Udd

  2. Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Linda L. Bachinski, Mario Sirito, Shodimu-Emmanuel Olufemi, Shohrae Hajibashi & Ralf Krahe

  3. University of Texas Graduate School of Biomedical Sciences, Houston, TX, 77030, USA

    Shohrae Hajibashi

  4. Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Keith A. Baggerly

  5. Graduate Program in Human and Molecular Genetics, University of Texas at Houston Graduate School of Biomedical Sciences, Houston, TX, 77030, USA

    Keith A. Baggerly & Ralf Krahe

  6. Neuromuscular Research, Department of Neurology, University Hospital of Tampere, 33520, Tampere, Finland

    Olayinka Raheem, Tiina Suominen & Bjarne Udd

  7. Department of Pathology, Center for Laboratory Medicine, Pirkanmaa Hospital District, 33520, Tampere, Finland

    Hannu Haapasalo

  8. Department of Pathology, University of Helsinki and University Hospital of Helsinki, 00014, Helsinki, Finland

    Anders Paetau & Hannu Kalimo

  9. Department of Molecular Biology and Biotechnologies, University of Milan, 20133, Milan, Italy

    Rosanna Cardani

  10. Department of Neurology, IRCCS Policlinico San Donato, University of Milan, San Donato Milanese, 20097, Milan, Italy

    Giovanni Meola

  11. Department of Clinical Neuroscience, Karolinska Institute, 17176, Stockholm, Sweden

    Lars Edström

  12. Graduate Program in Genes and Development, University of Texas at Houston Graduate School of Biomedical Sciences, Houston, TX, 77030, USA

    Ralf Krahe

  13. Department of Neurology, Vaasa Central Hospital, 65100, Vaasa, Finland

    Bjarne Udd

  14. Biomedicum Helsinki, Folkhälsan Institute of Genetics, Helsinki University, C304B, P.O. Box 63, 00014, Helsinki, Finland

    Bjarne Udd

  15. Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Ralf Krahe

Authors
  1. Anna Vihola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linda L. Bachinski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mario Sirito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shodimu-Emmanuel Olufemi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shohrae Hajibashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keith A. Baggerly
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Olayinka Raheem
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hannu Haapasalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tiina Suominen
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jeanette Holmlund-Hampf
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Anders Paetau
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rosanna Cardani
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Giovanni Meola
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Hannu Kalimo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Lars Edström
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ralf Krahe
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Bjarne Udd
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ralf Krahe or Bjarne Udd.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vihola, A., Bachinski, L.L., Sirito, M. et al. Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2. Acta Neuropathol 119, 465–479 (2010). https://doi.org/10.1007/s00401-010-0637-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-010-0637-6

Keywords

Search

Navigation