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01-08-2017 | Review

Biomolecular diagnosis of myotonic dystrophy type 2: a challenging approach

Authors: Giovanni Meola, Fiammetta Biasini, Rea Valaperta, Elena Costa, Rosanna Cardani

Published in: Journal of Neurology | Issue 8/2017

Abstract

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are the most common adult form of muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia, and multiorgan involvement. The onset and symptoms of the myotonic dystrophies are diverse, complicating their diagnoses and limiting a comprehensive approach to their clinical care. Diagnostic delay in DM2 is due not only to the heterogeneous phenotype and the aspecific onset but also to the unfamiliarity with the disorder by most clinicians. Moreover, the DM2 diagnostic odyssey is complicated by the difficulties to develop an accurate, robust, and cost-effective method for a routine molecular assay. The aim of this review is to underline by challenging approach the diagnostic limits and pitfalls that could results in failure to recognize the presence of DM2 disease. Understanding and preventing delays in DM2 diagnosis may facilitate family planning, improve symptom management in the short term, and facilitate more specific treatment in the long term.

Harper PS (2001) Myotonic dystrophy, 3rd edn. Saunders, London

Brook JD, McCurrach ME, Harley HG, Buckler AJ, Church D, Aburatani H, Hutnter K, Stanton VP, Thirion JP, Hudson T (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 68:799–808CrossRefPubMed

Fu YH, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258CrossRefPubMed

Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barceló J, O’Hoy K (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3′ untranslated region of the gene. Science 255:1253–1255CrossRefPubMed

Ranum LP, Rasmussen PF, Benzow KA, Koob MD, Day JW (1998) Genetic mapping of a second myotonic dystrophy locus. Nature Gen 19:196–198CrossRef

Liquori CL, Ricker K, Moseley ML, Jacobsen JFKW, Naylor SL, Day JW, Ranum LP (2001) Myotonic dystrophy type 2 caused by a CCTG expansion in intron 1 of ZNF9. Science 29:3864–3867

Meola G, Cardani R (2017) Myotonic dystrophy type 2 and modifier genes: an update on clinical and pathomolecular aspects. Neurol Sci. doi:10.1007/s10072-016-2805-5

Ricker K, Koch MC, Lehmann-Horn F, Pongratz D, Otto M, Heine R, Moxley RT 3rd (1994) Proximal myotonic myopathy: a new dominant disorder with myotonia, muscle weakness, and cataracts. Neurology 44:1448–1452CrossRefPubMed

Meola G, Sansone V, Radice S, Skradski S, Ptacek L (1996) A family with an unusual myotonic and myopathic phenotype and no CTG expansion (proximal myotonic myopathy syndrome): a challenge for future molecular studies. Neuromuscul Disord 6:143–150CrossRefPubMed

10.

Thornton CA, Griggs RC, Moxley RT 3rd (1994) Myotonic dystrophy with no trinucleotide repeat expansion. Ann Neurol 35:269–272CrossRefPubMed

11.

Udd B, Krahe R, Wallgren-Pettersson C, Falck B, Kalimo H (1997) Proximal myotonic dysrtrophy: a family with autosomal dominant muscular dystrophy, cataracts, hearing loss and hypogonadism: heterogeneity of proximal myotonic syndromes? Neuromuscul Disord 4:217–288CrossRef

12.

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 (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 73:835–848CrossRefPubMedPubMedCentral

13.

Timchenko LT, Miller JW, Timchenko NA, DeVore DR, Datar KV, Lin L, Roberts R, Caskey CT, Swanson MS (1996) Identification of a (CUG)n triplet repeat RNA-binding protein and its expression in myotonic dystrophy. Nucl Acids Res 24:4407–4414CrossRefPubMedPubMedCentral

14.

Miller JW, Urbinati CR, Teng-Umnuay P, Stenberg MG, Byrne BJ, Thornton CA, Swanson MS (2000) Recruitment of human muscleblind proteins to (CUG) (n) expansions associated with myotonic dystrophy. EMBO J 19:4439–4448CrossRefPubMedPubMedCentral

15.

Vihola A, Bachinski LL, Sirito M, Olufemi SE, Hajibashi S, Baggerly KA, Raheem O, Haapasalo H, Suominen T, Holmlund-Hampf J, Paetau A, Cardani R, Meola G, Kalimo H, Edström L, Krahe R, Udd B (2010) Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2. Acta Neuropathol 119:465–479CrossRefPubMedPubMedCentral

16.

Nakamori M, Sobczak K, Puwanant A, Welle S, Eichinger K, Pandya S, Dekdebrun J, Heatwole CR, McDermott MP, Chen T, Cline M, Tawil R, Osborne RJ, Wheeler TM, Swanson MS, Moxley RT 3rd, Thornton CA (2013) Splicing biomarkers of disease severity in myotonic dystrophy. Ann Neurol 74:862–872CrossRefPubMedPubMedCentral

17.

Perfetti A, Greco S, Fasanaro P, Bugiardini E, Cardani R, Manteiga JM, Riba M, Cittaro D, Stupka E, Meola G, Martelli F (2014) Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2. PLoS One 9:e93983CrossRefPubMedPubMedCentral

18.

Pelletier R, Hamel F, Beaulieu D, Patry L, Haineault C, Tarnopolsky M, Schoser B, Puymirat J (2009) Absence of a differentiation defect in muscle satellite cells from DM2 patients. Neurobiol Dis 36:181–190CrossRefPubMed

19.

Raheem O, Olufemi SE, Bachinski LL, Vihola A, Sirito M, Holmlund-Hampf J, Haapasalo H, Li YP, Udd B, Krahe R (2010) Mutant (CCTG)n expansion causes abnormal expression of Zinc finger protein 9 (ZNF9) in myotonic dystrophy type 2. Am J Pathol 177:3025–3036CrossRefPubMedPubMedCentral

20.

Cardani R, Bugiardini E, Renna LV, Rossi G, Colombo G, Valaperta R, Novelli G, Botta A, Meola G (2013) Overexpression of CUGBP1 in skeletal muscle from adult classic myotonic dystrophy type 1 but not from myotonic dystrophy type 2. PLoS One 8:e83777CrossRefPubMedPubMedCentral

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 29:9042–9049CrossRefPubMedPubMedCentral

22.

Salisbury E, Schoser B, Schneider-Gold C, Wang GL, Huichalaf C, Jin B, Sirito M, Sarkar P, Krahe R, Timchenko NA, Timchenko LT (2009) Expression of RNA CCUG repeats dysregulates translation and degradation of proteins in myotonic dystrophy 2 patients. Am J Pathol 175:748–762CrossRefPubMedPubMedCentral

23.

Gambardella S, Rinaldi F, Lepore SM, Vihola A, Loro E, Angelini C, Vergani L, Novelli G, Botta A (2010) Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients. J Transl Med 8:48–54CrossRefPubMedPubMedCentral

24.

Perbellini R, Greco S, Sarra-Ferraris G, Cardani R, Capogrossi MC, Meola G, Martelli F (2011) Dysregulation and cellular mislocalization of specific miRNAs in myotonic dystrophy type 1. Neuromuscul Disord 21:81–88CrossRefPubMed

25.

Greco S, Perfetti A, Fasanaro P, Cardani R, Capogrossi MC, Meola G, Martelli F (2012) Deregulated microRNAs in myotonic dystrophy type 2. PLoS One 7:e39732CrossRefPubMedPubMedCentral

26.

Zu T, Gibbensa B, Dotya NS, Gomes-Pereira M, Huguetd A, Stone MD, Margolis J, Petersong M, Markowski TW, Ingram MAC, Nan Z, Forster C, Low WC, Schoser B, Somia NV, Clark HB, Schmechel S, Bitterman PB, Gourdon G, Swanson MS, Moseley M, Ranum LPW (2011) Non-ATG—initiated translation directed by microsatellite expansions. Proc Natl Acad Sci USA 108:260–265CrossRefPubMed

27.

Zu T, Cleary J, Liu Y, Reid T, Banez-Coronel M, Xia G, Ashizawa T, Yachnis A, Ranum LPW (2013) RAN proteins from intronic CCTG expansions in DM2 patient brains. IDMC9, 16–19 Oct 2013, San Sebastian, Spain (Abstract)

28.

Hilbert JE, Ashizawa T, Day JW, Luebbe EA, Martens WB, McDermott MP, Tawil R, Thornton CA, Moxley RT 3rd (2013) Diagnostic odyssey of patients with myotonic dystrophy. J Neurol 260:2497–2504CrossRefPubMedPubMedCentral

29.

Suominen T, Bachinski LL, Auvinen S, Hackman P, Baggerly KA, Angelini C, Peltonen L, Krahe R, Udd B (2011) Population frequency of myotonic dystrophy: higher than expected frequency of myotonic dystrophy type 2 (DM2) mutation in Finland. Eur J Hum Genet 19:776–782CrossRefPubMedPubMedCentral

30.

Matsuura T, Minami N, Arahata H, Ohno K, Abe K, Hayashi YK, Nishino I (2012) Myotonic dystrophy type 2 is rare in the Japanese population. J Hum Genet 57:219–220CrossRefPubMed

31.

Day JW, Ricker K, Jacobsen JF, Rasmussen LJ, Dick KA, Kress WC, Koch MC, Beilman GJ, Harrison AR, Dalton JC, Ranum LP (2003) Myotonic dystrophy type 2: molecular, diagnostic and clinical spectrum

32.

Suominen T, Schoser B, Raheem O et al (2008) High frequency of co-segregating CLCN1 mutations among myotonic dystrophy type 2 patients from Finland and Germany. J Neurol 255:1731–1736CrossRefPubMedPubMedCentral

33.

Cardani R, Giagnacovo M, Botta A, Rinaldi F, Morgante A, Udd B, Raheem O, Penttilä S, Suominen T, Renna LV, Sansone V, Bugiardini E, Novelli G, Meola G (2012) Co-segregation of DM2 with a recessive CLCN1 mutation in juvenile onset of myotonic dystrophy type 2. J Neurol 259:2090–2099CrossRefPubMed

34.

Bugiardini E, Rivolta I, Binda A, Soriano Caminero A, Cirillo F, Cinti A, Giovannoni R, Botta A, Cardani R, Wicklund MP, Meola G (2015) SCN4A mutation as modifying factor of myotonic dystrophy type 2 phenotype. Neuromuscul Disord 25:301–307CrossRefPubMed

35.

Logigian EL, Ciafaloni E, Quinn LC, Dilek N, Pandya S, Moxley RT 3rd, Thornton CA (2007) Severity, type, and distribution of myotonic discharges are different in type 1 and type 2 myotonic dystrophy. Muscle Nerve 35(4):479–485CrossRefPubMed

36.

Gawel M, Szmidt-Salkowska E, Lusakowska A, Nojszewska M, Sulek A, Krysa W, Rajkiewicz M, Seroka A, Kaminska AM (2014) Value of short exercise and short exercise with cooling tests in the diagnosis of myotonic dystrophies (DM1 and DM2). Muscle Nerve 49(2):277–283CrossRefPubMed

37.

George A, Schneider-Gold C, Zier S, Reiners K, Sommer C (2004) Musculoskeletal pain in patients with myotonic dystrophy type 2. Arch Neurol 61:1938–1942PubMed

38.

Suokas KI, Haanpa¨a¨ M, Kautiainen H, Udd B, HietaHarju AJ (2012) Pain in patients with myotonic dystrophy type 2: a postal survey in Finland. Muscle Nerve 45:70–74CrossRefPubMed

39.

Peric M, Peric S, Rapajic N, Dobricic V, Savic-Pavicevic D, Nesic I, Radojicic S, Novakovic I, Lavrnic D, Rakocevic-Stojanovic V (2015) Multidimensional aspects of pain in myotonic dystrophies. Acta Myol 34:126–132PubMedPubMedCentral

40.

Sansone VA, Brigonzi E, Schoser B, Villani S, Gaeta M, De Ambroggi G, Bandera F, De Ambroggi L, Meola G (2013) The frequency and severity of cardiac involvement in myotonic dystrophy type 2 (DM2): long-term outcomes. Int J Cardiol 168:1147–1153CrossRefPubMed

41.

Lee TM, Maurer MS, Karbassi I, Braastad C, Batish SD, Chung WK (2012) Severe dilated cardiomyopathy in a patient with myotonic dystrophy type 2 and homozygous repeat expansion in ZNF9. Congest Heart Fail Greenwich Conn 18:183–186CrossRef

42.

Bhat S, Sander HW, Grewal RP, Chokroverty S (2012) Sleep disordered breathing and other sleep dysfunction in myotonic dystrophy type 2. Sleep Med 13:1207–1208CrossRefPubMed

43.

Chokroverty S, Bhat S, Rosen D, Farheen A (2012) REM behavior disorder in myotonic dystrophy type 2. Neurology 78:2004CrossRefPubMed

44.

Lam EM, Shepard PW, St Louis EK, Dueffert LG, Slocumb N, McCarter SJ, Silber MH, Boeve BF, Olson EJ, Somers VK, Milone M (2013) Restless legs syndrome and daytime sleepiness are prominent in myotonic dystrophy type 2. Neurology 81:157–164CrossRefPubMedPubMedCentral

45.

Passeri E, Bugiardini E, Sansone VA, Valaperta R, Costa E, Ambrosi B, Meola G, Corbetta S (2013) Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies. J Neurol Sci 331:132–135CrossRefPubMed

46.

Meola G, Sansone V, Perani D, Scarone S, Cappa S, Dragoni C, Cattaneo E, Cotelli M, Gobbo C, Fazio F, Siciliano G, Mancuso M, Vitelli E, Zhang S, Krahe R, Moxley RT (2003) Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2). Neuromuscul Disord 13:813–821CrossRefPubMed

47.

Schneider-Gold C, Bellenberg B, Prehn C, Krogias C, Schneider R, Klein J, Gold R, Lukas C (2015) Cortical and subcortical grey and white matter atrophy in myotonic dystrophies type 1 and 2 is associated with cognitive impairment, depression and daytime sleepiness. PLoS One 10:e0130352CrossRefPubMedPubMedCentral

48.

Peric S, Mandic-Stojmenovic G, Stefanova E, Savic-Pavicevic D, Pesovic J, Ilic V, Dobricic V, Basta I, Lavrnic D, Rakocevic-Stojanovic V (2015) Frontostriatal dysexecutive syndrome: a core cognitive feature of myotonic dystrophy type 2. J Neurol 262:142–148CrossRefPubMed

49.

Tieleman AA, Knuijt S, van Vliet J, de Swart BJ, Ensink R, van Engelen BG (2009) Dysphagia is present but mild in myotonic dystrophy type 2. Neuromuscul Disord 19:196–198CrossRefPubMed

50.

Newman B, Meola G, O’Donovan DG, Schapira AH, Kingston H (1999) Proximal myotonic myopathy (PROMM) presenting as myotonia during pregnancy. Neuromuscul Disord 9:144–149CrossRefPubMed

51.

Liquori CL, Ikeda Y, Weatherspoon M, Ricker K, Schoser BG, Dalton JC, Day JW, Ranum LP (2003) Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract. Am J Hum Genet 73:849–862CrossRefPubMedPubMedCentral

52.

Bachinski LL, Czernuszewicz T, Ramagli LS, Suominen T, Shriver MD, Udd B, Siciliano MJ, Krahe R (2009) Premutation allele pool in myotonic dystrophy type 2. Neurology 72:490–497CrossRefPubMedPubMedCentral

53.

Kurosaki T, Ueda S, Ishida T, Abe K, Ohno K, Matsuura T (2012) The unstable CCTG repeat responsible for myotonic dystrophy type 2 originates from an AluSx element insertion into an early primate genome. PLoS One 7:e38379CrossRefPubMedPubMedCentral

54.

Guo P, Lam SL (2015) New insights into the genetic instability in CCTG repeats. FEBS Lett 589:3058–3063CrossRefPubMed

55.

Wong LJ, Ashizawa T, Monckton DG, Caskey CT, Richards CS (1995) Somatic heterogeneity of the CTG repeat in myotonic dystrophy is age and size dependent. Am J Hum Genet 56:114–122PubMedPubMedCentral

56.

Monckton DG, Wong LI, Ashizawa T, Caskey CT (1995) Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses. Hum Mol Genet 4:1–8CrossRefPubMed

57.

Schneider C, Ziegler A, Ricker K, Grimm T, Kress W, Reimers CD, Meinck H, Reiners K, Toyka KV (2000) Proximal myotonic myopathy: evidence for anticipation in families with linkage to chromosome 3q. Neurology 3:383–388CrossRef

58.

Schoser BG, Kress W, Walter MC, Halliger-Keller B, Lochmuller H, Ricker K (2004) Homozygosity for CCTG mutation in myotonic dystrophy type 2. Brain 127:1868–1877CrossRefPubMed

59.

Kamsteeg EJ, Kress W, Catalli C, Hertz JM, Witsch-Baumgartner M, Buckley MF, van Engelen BG, Schwartz M, Scheffer H (2002) Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2. Eur J Hum Genet 20:1203–1208CrossRef

60.

Bonifazi E, Vallo L, Giardina E, Botta A, Novelli G (2004) A long PCR-based molecular protocol for detecting normal and expanded ZNF9 alleles in myotonic dystrophy type 2. Diagn Mol Pathol 13:164–166PubMed

61.

Valaperta R, Lombardi F, Cardani R, Fossati B, Brigonzi E, Merli I, Sansone V, Merletti G, Spina E, Meola G, Costa E (2015) Development and validation of a new molecular diagnostic assay for detection of myotonic dystrophy type 2. Genet Test Mol Biomark 19:703–709CrossRef

62.

Warner JP, Barron LH, Goudie D, Kelly K, Dow D, Fitzpatrick DR, Brock DJ (1996) A general method for the detection of large CAG repeat expansions by fluorescent PCR. J Med Genet 33:1022–1026CrossRefPubMedPubMedCentral

63.

Falk M, Vojtiskova M, Lukas Z, Kroupova I, Froster U (2006) Simple procedure for automatic detection of unstable alleles in the myotonic dystrophy and Huntington’s disease loci. Genet Test 10:85–97CrossRefPubMed

64.

Catalli C, Morgante A, Iraci R, Rinaldi F, Botta A, Novelli G (2010) Validation of sensitivity and specificity of tetraplet primed PCR (TP-PCR) in the molecular diagnosis of myotonic dystrophy type 2. J Mol Diagn 12:601–606CrossRefPubMedPubMedCentral

65.

Meola G, Bugiardini E, Cardani R (2012) Muscle biopsy. J Neurol 259:601–610CrossRefPubMed

66.

Staron RS, Hagerman FC, Hikida RS, Murray TF, Hostler DP, Crill MT, Ragg KE, Toma K (2000) Fiber type composition of the vastus lateralis muscle of young men and women. J Histochem Cytochem 48:623–629CrossRefPubMed

67.

Schiaffino S, Reggiani C (2011) Fiber types in mammalian skeletal muscles. Physiol Rev 91:1447–1531CrossRefPubMed

68.

Hiton-Jones D, Squier M, Taylor D, Matthews P (1995) Metabolic Myopathies. Major problems in neurology. W.B. Saunders Ltd, Philadelphia, pp 30–54

69.

Vihola A, Bassez G, Meola G, Zhang S, Haapasalo H, Paetau A, Mancinelli E, Rouche A, Hogrel JY, Laforêt P, Maisonobe T, Pellissier JF, Krahe R, Eymard B, Udd B (2003) Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. Neurology 60:1854–1857CrossRefPubMed

70.

Bassez G, Chapoy E, Bastuji-Garin S, Radvanyi-Hoffman H, Authier FJ, Pellissier JF, Eymard B, Gherardi RK (2008) Type 2 myotonic dystrophy can be predicted by the combination of type 2 muscle fiber central nucleation and scattered atrophy. J Neuropathol Exp Neurol 67:319–325CrossRefPubMed

71.

Pisani V, Panico MB, Terracciano C, Bonifazi E, Meola G, Novelli G, Bernardi G, Angelini C, Massa R (2008) Preferential central nucleation of type 2 myofibers is an invariable feature of myotonic dystrophy type 2. Muscle Nerve 38(5):1405–1411CrossRefPubMed

72.

Cardani R, Mancinelli E, Sansone V, Rotondo G, Meola G (2004) Biomolecular identification of (CCTG)n mutation in myotonic dystrophy type 2 (DM2) by FISH on muscle biopsy. Eur J Histochem 48:437–442CrossRefPubMed

73.

Sallinen R, Vihola A, Bachinski LL, Huoponen K, Haapasalo H, Hackman P, Zhang S, Sirito M, Kalimo H, Meola G, Horelli-Kuitunen N, Wessman M, Krahe R, Udd B (2004) New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2). Neuromuscul Disord 14:274–283CrossRefPubMed

74.

Cardani R, Mancinelli E, Giagnacovo M, Sansone V, Meola G (2009) Ribonuclear inclusions as biomarker of myotonic dystrophy type 2, even in improperly frozen or defrozen skeletal muscle biopsies. Eur J Histochem 53:107–112CrossRefPubMed

75.

Lucchiari S, Pagliarani S, Corti S, Mancinelli E, Servida M, Fruguglietti E, Sansone V, Moggio M, Bresolin N, Comi GP, Meola G (2008) Colocalization of ribonuclear inclusions with muscle blind like-proteins in a family with myotonic dystrophy type 2 associated with a short CCTG expansion. J Neurol Sci 275:159–163CrossRefPubMed

76.

Nguyen L, Lee J, Wong CH, Zimmerman SC (2014) Small molecules that target the toxic RNA in myotonic dystrophy type 2. Chem Med Chem 9:2455–2462CrossRefPubMedPubMedCentral

77.

Wojtkowiak-Szlachcic A, Taylor K, Stepniak-Konieczna E, Sznajder LJ, Mykowska A, Sroka J, Thornton CA, Sobczak K (2015) Short antisense-locked nucleic acids (all-LNAs) correct alternative splicing abnormalities in myotonic dystrophy. Nucleic Acids Res 43(6):3318–3331

78.

Wheeler TM, Leger AJ, Pandey SK, MacLeod AR, Nakamori M, Cheng SH, Wentworth BM, Bennett CF, Thornton CA (2012) Targeting nuclear RNA for in vivo correction of myotonic dystrophy. Nature 488(7409):111–115CrossRefPubMedPubMedCentral

79.

Sobczak K, Wheeler TM, Wang W, Thornton CA (2013) RNA interference targeting CUG repeats in a mouse model of myotonic dystrophy. Mol Ther 21(2):380–387CrossRefPubMed

80.

Leger AJ, Mosquea LM, Clayton NP, Wu IH, Weeden T, Nelson CA, Phillips L, Roberts E, Piepenhagen PA, Cheng SH, Wentworth BM (2013) Systemic delivery of a peptide-linked morpholino oligonucleotide neutralizes mutant RNA toxicity in a mouse model of myotonic dystrophy. Nucleic Acid Ther 23(2):109–117CrossRefPubMed

Title: Biomolecular diagnosis of myotonic dystrophy type 2: a challenging approach
Authors: Giovanni Meola
Fiammetta Biasini
Rea Valaperta
Elena Costa
Rosanna Cardani
Publication date: 01-08-2017
Publisher: Springer Berlin Heidelberg
Published in: Journal of Neurology / Issue 8/2017
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-017-8504-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Biomolecular diagnosis of myotonic dystrophy type 2: a challenging approach

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Keynote webinar | Spotlight on medication adherence

Springer Medicine

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