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Muscular dystrophies: an update on pathology and diagnosis

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Abstract

Muscular dystrophies are clinically, genetically, and molecularly a heterogeneous group of neuromuscular disorders. Considerable advances have been made in recent years in the identification of causative genes, the differentiation of the different forms and in broadening the understanding of pathogenesis. Muscle pathology has an important role in these aspects, but correlation of the pathology with clinical phenotype is essential. Immunohistochemistry has a major role in differential diagnosis, particularly in recessive forms where an absence or reduction in protein expression can be detected. Several muscular dystrophies are caused by defects in genes encoding sarcolemmal proteins, several of which are known to interact. Others are caused by defects in nuclear membrane proteins or enzymes. Assessment of both primary and secondary abnormalities in protein expression is useful, in particular the hypoglycosylation of alpha-dystroglycan. In dominantly inherited muscular dystrophies it is rarely possible to detect a change in the expression of the primary defective protein; an exception to this is caveolin-3.

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References

  1. Allamand V, Richard P, Lescure A, Ledeuil C, Desjardin D, Petit N, Gartioux C, Ferreiro A, Krol A, Pellegrini N, Urtizberea JA, Guicheney P (2006) A single homozygous point mutation in a 3’untranslated region motif of selenoprotein N mRNA causes SEPN1-related myopathy. EMBO Rep 7:450–454

    PubMed  CAS  Google Scholar 

  2. Anderson LV, Harrison RM, Pogue R, Vafiadaki E, Pollitt C, Davison K, Moss JA, Keers S, Pyle A, Shaw PJ, Mahjneh I, Argov Z, Greenberg CR, Wrogemann K, Bertorini T, Goebel HH, Beckmann JS, Bashir R, Bushby KM (2000) Secondary reduction in calpain 3 expression in patients with limb girdle muscular dystrophy type 2B and Miyoshi myopathy (primary dysferlinopathies). Neuromuscul Disord 10:553–559

    Article  PubMed  CAS  Google Scholar 

  3. Askanas V, Serdaroglu P, Engel WK, Alvarez RB (1991) Immunolocalization of ubiquitin in muscle biopsies of patients with inclusion body myositis and oculopharyngeal muscular dystrophy. Neurosci Lett 130:73–76

    Article  PubMed  CAS  Google Scholar 

  4. Baumeister SK, Todorovic S, Milic-Rasic V, Dekomien G, Lochmuller H, Walter MC (2009) Eosinophilic myositis as presenting symptom in gamma-sarcoglycanopathy. Neuromuscul Disord 19:167–171

    Article  PubMed  Google Scholar 

  5. Becher MW, Kotzuk JA, Davis LE, Bear DG (2000) Intranuclear inclusions in oculopharyngeal muscular dystrophy contain poly(A) binding protein 2. Ann Neurol 48:812–815

    Article  PubMed  CAS  Google Scholar 

  6. Bolduc V, Marlow G, Boycott KM, Saleki K, Inoue H, Kroon J, Itakura M, Robitaille Y, Parent L, Baas F, Mizuta K, Kamata N, Richard I, Linssen WH, Mahjneh I, de Viller M, Bashir R, Brais B (2010) Recessive mutations in the putative calcium-activated chloride channel Anoctamin 5 cause proximal LGMD2L and distal MMD3 muscular dystrophies. Am J Hum Genet 86:213–221

    Article  PubMed  CAS  Google Scholar 

  7. Brais B (2009) Oculopharyngeal muscular dystrophy: a polyalanine myopathy. Curr Neurol Neurosci Rep 9:76–82

    Article  PubMed  CAS  Google Scholar 

  8. Brockington M, Brown SC, Lampe A, Yuva Y, Feng L, Jimenez-Mallebrera C, Sewry CA, Flanigan KM, Bushby K, Muntoni F (2004) Prenatal diagnosis of Ullrich congenital muscular dystrophy using haplotype analysis and collagen VI immunocytochemistry. Prenat Diagn 24:440–444

    Article  PubMed  Google Scholar 

  9. Brown SC, Torelli S, Brockington M, Yuva Y, Jimenez C, Feng L, Anderson L, Ugo I, Kroger S, Bushby K, Voit T, Sewry C, Muntoni F (2004) Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD2I muscular dystrophies. Am J Pathol 164:727–737

    PubMed  CAS  Google Scholar 

  10. Bushby K (2009) Diagnosis and management of the limb girdle muscular dystrophies. Pract Neurol 9:314–323

    Article  PubMed  Google Scholar 

  11. Bushby K, Anderson LV, Pollitt C, Naom I, Muntoni F, Bindoff L (1998) Abnormal merosin in adults. A new form of late onset muscular dystrophy not linked to chromosome 6q2. Brain 121(Pt 4):581–588

    Article  PubMed  Google Scholar 

  12. Calado A, Tome FM, Brais B, Rouleau GA, Kuhn U, Wahle E, Carmo-Fonseca M (2000) Nuclear inclusions in oculopharyngeal muscular dystrophy consist of poly(A) binding protein 2 aggregates which sequester poly(A) RNA. Hum Mol Genet 9:2321–2328

    PubMed  CAS  Google Scholar 

  13. Carbone I, Bruno C, Sotgia F, Bado M, Broda P, Masetti E, Panella A, Zara F, Bricarelli FD, Cordone G, Lisanti MP, Minetti C (2000) Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia. Neurology 54:1373–1376

    PubMed  CAS  Google Scholar 

  14. Charlton R, Henderson M, Richards J, Hudson J, Straub V, Bushby K, Barresi R (2009) Immunohistochemical analysis of calpain 3: advantages and limitations in diagnosing LGMD2A. Neuromuscul Disord 19:449–457

    Article  PubMed  Google Scholar 

  15. Confalonieri P, Oliva L, Andreetta F, Lorenzoni R, Dassi P, Mariani E, Morandi L, Mora M, Cornelio F, Mantegazza R (2003) Muscle inflammation and MHC class I up-regulation in muscular dystrophy with lack of dysferlin: an immunopathological study. J Neuroimmunol 142:130–136

    Article  PubMed  CAS  Google Scholar 

  16. Darin N, Kroksmark AK, Ahlander AC, Moslemi AR, Oldfors A, Tulinius M (2007) Inflammation and response to steroid treatment in limb-girdle muscular dystrophy 2I. Eur J Paediatr Neurol 11:353–357

    Article  PubMed  CAS  Google Scholar 

  17. Dubowitz V, Sewry CA (2007) Muscle biopsy: a practical approach 3rd edn, Elsevier

  18. Fidzianska A, Rowinska-Marcinska K, Hausmanowa-Petrusewicz I (2004) Coexistence of X-linked recessive Emery-Dreifuss muscular dystrophy with inclusion body myositis-like morphology. Acta Neuropathol 107:197–203

    Article  PubMed  Google Scholar 

  19. Foroud T, Pankratz N, Batchman AP, Pauciulo MW, Vidal R, Miravalle L, Goebel HH, Cushman LJ, Azzarelli B, Horak H, Farlow M, Nichols WC (2005) A mutation in myotilin causes spheroid body myopathy. Neurology 65:1936–1940

    Article  PubMed  CAS  Google Scholar 

  20. Gazzerro E, Sotgia F, Bruno C, Lisanti MP, Minetti C (2010) Caveolinopathies: from the biology of caveolin-3 to human diseases. Eur J Hum Genet 18:137–145

    Article  PubMed  CAS  Google Scholar 

  21. Godfrey C, Escolar D, Brockington M, Clement EM, Mein R, Jimenez-Mallebrera C, Torelli S, Feng L, Brown SC, Sewry CA, Rutherford M, Shapira Y, Abbs S, Muntoni F (2006) Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann Neurol 60:603–610

    Article  PubMed  CAS  Google Scholar 

  22. Gueneau L, Bertrand AT, Jais JP, Salih MA, Stojkovic T, Wehnert M, Hoeltzenbein M, Spuler S, Saitoh S, Verschueren A, Tranchant C, Beuvin M, Lacene E, Romero NB, Heath S, Zelenika D, Voit T, Eymard B, Ben YR, Bonne G (2009) Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am J Hum Genet 85:338–353

    Article  PubMed  CAS  Google Scholar 

  23. Guglieri M, Straub V, Bushby K, Lochmuller H (2008) Limb-girdle muscular dystrophies. Curr Opin Neurol 21:576–584

    Article  PubMed  CAS  Google Scholar 

  24. Hackman JP, Vihola AK, Udd AB (2003) The role of titin in muscular disorders. Ann Med 35:434–441

    Article  PubMed  CAS  Google Scholar 

  25. Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B (2002) Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet 71:492–500

    Article  PubMed  CAS  Google Scholar 

  26. Haravuori H, Vihola A, Straub V, Auranen M, Richard I, Marchand S, Voit T, Labeit S, Somer H, Peltonen L, Beckmann JS, Udd B (2001) Secondary calpain3 deficiency in 2q-linked muscular dystrophy: titin is the candidate gene. Neurology 56:869–877

    PubMed  CAS  Google Scholar 

  27. Hayashi YK, Matsuda C, Ogawa M, Goto K, Tominaga K, Mitsuhashi S, Park YE, Nonaka I, Hino-Fukuyo N, Haginoya K, Sugano H, Nishino I (2009) Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest 119:2623–2633

    Article  PubMed  CAS  Google Scholar 

  28. Jimenez-Mallebrera C, Maioli MA, Kim J, Brown SC, Feng L, Lampe AK, Bushby K, Hicks D, Flanigan KM, Bonnemann C, Sewry CA, Muntoni F (2006) A comparative analysis of collagen VI production in muscle, skin and fibroblasts from 14 Ullrich congenital muscular dystrophy patients with dominant and recessive COL6A mutations. Neuromuscul Disord 16:571–582

    Article  PubMed  CAS  Google Scholar 

  29. Jimenez-Mallebrera C, Torelli S, Feng L, Kim J, Godfrey C, Clement E, Mein R, Abbs S, Brown SC, Campbell KP, Kroger S, Talim B, Topaloglu H, Quinlivan R, Roper H, Childs AM, Kinali M, Sewry CA, Muntoni F (2009) A comparative study of alpha-dystroglycan glycosylation in dystroglycanopathies suggests that the hypoglycosylation of alpha-dystroglycan does not consistently correlate with clinical severity. Brain Pathol 19:596–611

    Article  PubMed  CAS  Google Scholar 

  30. Kang PB, Feener CA, Estrella E, Thorne M, White AJ, Darras BT, Amato AA, Kunkel LM (2007) LGMD2I in a North American population. BMC Musculoskelet Disord 8:115

    Article  PubMed  CAS  Google Scholar 

  31. Keramaris-Vrantsis E, Lu PJ, Doran T, Zillmer A, Ashar J, Esapa CT, Benson MA, Blake DJ, Rosenfeld J, Lu QL (2007) Fukutin-related protein localizes to the Golgi apparatus and mutations lead to mislocalization in muscle in vivo. Muscle Nerve 36:455–465

    Article  PubMed  CAS  Google Scholar 

  32. Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, Guglieri M, Ashton E, Abbs S, Nihoyannopoulos P, Garralda ME, Rutherford M, McCulley C, Popplewell L, Graham IR, Dickson G, Wood MJ, Wells DJ, Wilton SD, Kole R, Straub V, Bushby K, Sewry C, Morgan JE, Muntoni F (2009) Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol 8:918–928

    Article  PubMed  CAS  Google Scholar 

  33. Klinge L, Dekomien G, Aboumousa A, Charlton R, Epplen JT, Barresi R, Bushby K, Straub V (2008) Sarcoglycanopathies: can muscle immunoanalysis predict the genotype? Neuromuscul Disord 18:934–941

    Article  PubMed  Google Scholar 

  34. Konieczny P, Fuchs P, Reipert S, Kunz WS, Zeold A, Fischer I, Paulin D, Schroder R, Wiche G (2008) Myofiber integrity depends on desmin network targeting to Z-disks and costameres via distinct plectin isoforms. J Cell Biol 181:667–681

    Article  PubMed  CAS  Google Scholar 

  35. Krahn M, de Lopez MA, Streichenberger N, Bernard R, Pecheux C, Testard H, Pena-Segura JL, Yoldi E, Cabello A, Romero NB, Poza JJ, Bouillot-Eimer S, Ferrer X, Goicoechea M, Garcia-Bragado F, Leturcq F, Urtizberea JA, Levy N (2006) CAPN3 mutations in patients with idiopathic eosinophilic myositis. Ann Neurol 59:905–911

    Article  PubMed  CAS  Google Scholar 

  36. Lampe AK, Bushby KM (2005) Collagen VI related muscle disorders. J Med Genet 42:673–685

    Article  PubMed  CAS  Google Scholar 

  37. Lee JE, Cooper TA (2009) Pathogenic mechanisms of myotonic dystrophy. Biochem Soc Trans 37:1281–1286

    Article  PubMed  CAS  Google Scholar 

  38. Lo HP, Cooper ST, Evesson FJ, Seto JT, Chiotis M, Tay V, Compton AG, Cairns AG, Corbett A, MacArthur DG, Yang N, Reardon K, North KN (2008) Limb-girdle muscular dystrophy: diagnostic evaluation, frequency and clues to pathogenesis. Neuromuscul Disord 18:34–44

    Article  PubMed  Google Scholar 

  39. Manilal S, Sewry CA, Pereboev A, Man N, Gobbi P, Hawkes S, Love DR, Morris GE (1999) Distribution of emerin and lamins in the heart and implications for Emery-Dreifuss muscular dystrophy. Hum Mol Genet 8:353–359

    Article  PubMed  CAS  Google Scholar 

  40. Massa R, Panico MB, Caldarola S, Fusco FR, Sabatelli P, Terracciano C, Botta A, Novelli G, Bernardi G, Loreni F (2010) The myotonic dystrophy type 2 (DM2) gene product zinc finger protein 9 (ZNF9) is associated with sarcomeres and normally localized in DM2 patients’ muscles. Neuropathol Appl Neurobiol 36:275–284

    Article  PubMed  CAS  Google Scholar 

  41. Matsuda C, Hayashi YK, Ogawa M, Aoki M, Murayama K, Nishino I, Nonaka I, Arahata K, Brown RH Jr (2001) The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum Mol Genet 10:1761–1766

    Article  PubMed  CAS  Google Scholar 

  42. McMillan JR, Akiyama M, Rouan F, Mellerio JE, Lane EB, Leigh IM, Owaribe K, Wiche G, Fujii N, Uitto J, Eady RA, Shimizu H (2007) Plectin defects in epidermolysis bullosa simplex with muscular dystrophy. Muscle Nerve 35:24–35

    Article  PubMed  CAS  Google Scholar 

  43. Moreira ES, Wiltshire TJ, Faulkner G, Nilforoushan A, Vainzof M, Suzuki OT, Valle G, Reeves R, Zatz M, Passos-Bueno MR, Jenne DE (2000) Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 24:163–166

    Article  PubMed  CAS  Google Scholar 

  44. Morris GE (2001) The role of the nuclear envelope in Emery-Dreifuss muscular dystrophy. Trends Mol Med 7:572–577

    Article  PubMed  CAS  Google Scholar 

  45. Muchir A, van Engelen BG, Lammens M, Mislow JM, McNally E, Schwartz K, Bonne G (2003) Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp Cell Res 291:352–362

    Article  PubMed  CAS  Google Scholar 

  46. Muller HD, Landeghem FK, Schmidt PF, Sommer C, Goebel HH (2009) Macrophagic myofasciitis plus (distinct types of muscular dystrophy). Neuropediatrics 40:174–178

    Article  PubMed  CAS  Google Scholar 

  47. Muntoni F, Bonne G, Goldfarb LG, Mercuri E, Piercy RJ, Burke M, Yaou RB, Richard P, Recan D, Shatunov A, Sewry CA, Brown SC (2006) Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain 129:1260–1268

    Article  PubMed  CAS  Google Scholar 

  48. Muntoni F, Brockington M, Godfrey C, Ackroyd M, Robb S, Manzur A, Kinali M, Mercuri E, Kaluarachchi M, Feng L, Jimenez-Mallebrera C, Clement E, Torelli S, Sewry CA, Brown SC (2007) Muscular dystrophies due to defective glycosylation of dystroglycan. Acta Myol 26:129–135

    PubMed  CAS  Google Scholar 

  49. Muntoni F, Brockington M, Torelli S, Brown SC (2004) Defective glycosylation in congenital muscular dystrophies. Curr Opin Neurol 17:205–209

    Article  PubMed  CAS  Google Scholar 

  50. Muntoni F, Voit T (2004) The congenital muscular dystrophies in 2004: a century of exciting progress. Neuromuscul Disord 14:635–649

    Article  PubMed  Google Scholar 

  51. Nonaka I, Noguchi S, Nishino I (2005) Distal myopathy with rimmed vacuoles and hereditary inclusion body myopathy. Curr Neurol Neurosci Rep 5:61–65

    Article  PubMed  CAS  Google Scholar 

  52. Ognibene A, Sabatelli P, Petrini S, Squarzoni S, Riccio M, Santi S, Villanova M, Palmeri S, Merlini L, Maraldi NM (1999) Nuclear changes in a case of X-linked Emery-Dreifuss muscular dystrophy. Muscle Nerve 22:864–869

    Article  PubMed  CAS  Google Scholar 

  53. Olive M, Shatunov A, Gonzalez L, Carmona O, Moreno D, Quereda LG, Martinez-Matos JA, Goldfarb LG, Ferrer I (2008) Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2G in a European patient. Neuromuscul Disord 18:929–933

    Article  PubMed  Google Scholar 

  54. Perdoni F, Malatesta M, Cardani R, Giagnacovo M, Mancinelli E, Meola G, Pellicciari C (2009) RNA/MBNL1-containing foci in myoblast nuclei from patients affected by myotonic dystrophy type 2: an immunocytochemical study. Eur J Histochem 53:151–158

    PubMed  CAS  Google Scholar 

  55. Poppe M, Cree L, Bourke J, Eagle M, Anderson LV, Birchall D, Brockington M, Buddles M, Busby M, Muntoni F, Wills A, Bushby K (2003) The phenotype of limb-girdle muscular dystrophy type 2I. Neurology 60:1246–1251

    PubMed  CAS  Google Scholar 

  56. Pulkkinen L, Smith FJ, Shimizu H, Murata S, Yaoita H, Hachisuka H, Nishikawa T, McLean WH, Uitto J (1996) Homozygous deletion mutations in the plectin gene (PLEC1) in patients with epidermolysis bullosa simplex associated with late-onset muscular dystrophy. Hum Mol Genet 5:1539–1546

    Article  PubMed  CAS  Google Scholar 

  57. Quijano-Roy S, Mbieleu B, Bonnemann CG, Jeannet PY, Colomer J, Clarke NF, Cuisset JM, Roper H, De ML, D’Amico A, Ben YR, Nascimento A, Barois A, Demay L, Bertini E, Ferreiro A, Sewry CA, Romero NB, Ryan M, Muntoni F, Guicheney P, Richard P, Bonne G, Estournet B (2008) De novo LMNA mutations cause a new form of congenital muscular dystrophy. Ann Neurol 64:177–186

    Article  PubMed  Google Scholar 

  58. Rajab A, Straub V, McCann LJ, Seelow D, Varon R, Barresi R, Schulze A, Lucke B, Lutzkendorf S, Karbasiyan M, Bachmann S, Spuler S, Schuelke M (2010) Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet 6:e1000874

    Article  PubMed  CAS  Google Scholar 

  59. Randles KN, Lam lT, Sewry CA, Puckelwartz M, Furling D, Wehnert M, McNally EM, Morris GE (2010) Nesprins, but not sun proteins, switch isoforms at the nuclear envelope during muscle development. Dev Dyn 239:998–1009

    Article  PubMed  CAS  Google Scholar 

  60. Reilich P, Schramm N, Schoser B, Schneiderat P, Strigl-Pill N, Muller-Hocker J, Kress W, Ferbert A, Rudnik-Schoneborn S, Noth J, Lochmuller H, Weis J, Walter MC (2010) Facioscapulohumeral muscular dystrophy presenting with unusual phenotypes and atypical morphological features of vacuolar myopathy. J Neurol 257:1108–1118

    Google Scholar 

  61. Rosales XQ, Gastier-Foster JM, Lewis S, Vinod M, Thrush DL, Astbury C, Pyatt R, Reshmi S, Sahenk Z, Mendell JR (2010) Novel diagnostic features of dysferlinopathies. Muscle Nerve 42:14–21

    Article  PubMed  Google Scholar 

  62. Roux KJ, Burke B (2007) Nuclear envelope defects in muscular dystrophy. Biochim Biophys Acta 1772:118–127

    PubMed  CAS  Google Scholar 

  63. Schoser B, Goebel HH, Janisch I, Quasthoff S, Rother J, Bergmann M, Muller-Felber W, Windpassinger C (2009) Consequences of mutations within the C terminus of the FHL1 gene. Neurology 73:543–551

    Article  PubMed  CAS  Google Scholar 

  64. Schoser BG, Frosk P, Engel AG, Klutzny U, Lochmuller H, Wrogemann K (2005) Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H. Ann Neurol 57:591–595

    Article  PubMed  CAS  Google Scholar 

  65. Schoser BG, Schneider-Gold C, Kress W, Goebel HH, Reilich P, Koch MC, Pongratz DE, Toyka KV, Lochmuller H, Ricker K (2004) Muscle pathology in 57 patients with myotonic dystrophy type 2. Muscle Nerve 29:275–281

    Article  PubMed  Google Scholar 

  66. Schulte-Mattler WJ, Kley RA, Rothenfusser-Korber E, Bohm S, Bruning T, Hackemann J, Steinbrecher A, During MV, Voss B, Vorgerd M (2005) Immune-mediated rippling muscle disease. Neurology 64:364–367

    PubMed  CAS  Google Scholar 

  67. Selcen D, Engel AG (2004) Mutations in myotilin cause myofibrillar myopathy. Neurology 62:1363–1371

    PubMed  CAS  Google Scholar 

  68. Sewry CA, Jimenez- Mallebrera C, Brown SC, Muntoni F (2008) Diseases of muscle. In: Love S, Louis DN, Ellison D (eds) Greenfield’s Neuropathology 8th edition. Hodder Arnold. 1725–1820

  69. Sewry CA (2008) Pathological defects in congenital myopathies. J.Muscle Res.Cell Motil. 29:231–238

    Article  PubMed  Google Scholar 

  70. Sewry CA, Brown SC, Mercuri E, Bonne G, Feng L, Camici G, Morris GE, Muntoni F (2001) Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations. Neuropathol Appl Neurobiol 27:281–290

    Article  PubMed  CAS  Google Scholar 

  71. Sewry CA, Jimenez-Mallebrera C, Muntoni F (2008) Congenital myopathies. Curr Opin Neurol 21:569–575

    Article  PubMed  Google Scholar 

  72. Sewry CA, Muntoni F (1999) Inherited disorders of the extracellular matrix. Curr Opin Neurol 12:519–526

    Article  PubMed  CAS  Google Scholar 

  73. Sewry CA, Naom I, D’alessandro M, Sorokin L, Bruno S, Wilson LA, Dubowitz V, Muntoni F (1997) Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin alpha 2 chain. Neuromuscul Disord 7:169–175

    Article  PubMed  CAS  Google Scholar 

  74. Sewry CA, Philpot J, Sorokin LM, Wilson LA, Naom I, Goodwin F, D’alessandro M, Dubowitz V, Muntoni F (1996) Diagnosis of merosin (laminin-2) deficient congenital muscular dystrophy by skin biopsy. Lancet 347:582–584

    Article  PubMed  CAS  Google Scholar 

  75. Simha V, Garg A (2009) Inherited lipodystrophies and hypertriglyceridemia. Curr Opin Lipidol 20:300–308

    Article  PubMed  CAS  Google Scholar 

  76. Smith FJ, Eady RA, Leigh IM, McMillan JR, Rugg EL, Kelsell DP, Bryant SP, Spurr NK, Geddes JF, Kirtschig G, Milana G, de Bono AG, Owaribe K, Wiche G, Pulkkinen L, Uitto J, McLean WH, Lane EB (1996) Plectin deficiency results in muscular dystrophy with epidermolysis bullosa. Nat Genet 13:450–457

    Article  PubMed  CAS  Google Scholar 

  77. Tidball JG, Villalta SA (2010) Regulatory interactions between muscle and the immune system during muscle regeneration. Am J Physiol Regul Integr Comp Physiol [Epub ahead of print]

  78. Tunnah D, Sewry CA, Vaux D, Schirmer EC, Morris GE (2005) The apparent absence of lamin B1 and emerin in many tissue nuclei is due to epitope masking. J Mol Histol 36:337–344

    Article  PubMed  CAS  Google Scholar 

  79. Udd B, Vihola A, Sarparanta J, Richard I, Hackman P (2005) Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2 J. Neurology 64:636–642

    PubMed  CAS  Google Scholar 

  80. Uitto J, Pulkkinen L, Smith FJ, McLean WH (1996) Plectin and human genetic disorders of the skin and muscle. The paradigm of epidermolysis bullosa with muscular dystrophy. Exp Dermatol 5:237–246

    Article  PubMed  CAS  Google Scholar 

  81. Vainzof M, Anderson LV, McNally EM, Davis DB, Faulkner G, Valle G, Moreira ES, Pavanello RC, Passos-Bueno MR, Zatz M (2001) Dysferlin protein analysis in limb-girdle muscular dystrophies. J Mol Neurosci 17:71–80

    Article  PubMed  CAS  Google Scholar 

  82. Vainzof M, Passos-Bueno MR, Canovas M, Moreira ES, Pavanello RC, Marie SK, Anderson LV, Bonnemann CG, McNally EM, Nigro V, Kunkel LM, Zatz M (1996) The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies. Hum Mol Genet 5:1963–1969

    Article  PubMed  CAS  Google Scholar 

  83. Vainzof M, Richard P, Herrmann R, Jimenez-Mallebrera C, Talim B, Yamamoto LU, Ledeuil C, Mein R, Abbs S, Brockington M, Romero NB, Zatz M, Topaloglu H, Voit T, Sewry C, Muntoni F, Guicheney P, Tome FM (2005) Prenatal diagnosis in laminin alpha2 chain (merosin)-deficient congenital muscular dystrophy: a collective experience of five international centers. Neuromuscul Disord 15:588–594

    Article  PubMed  Google Scholar 

  84. Weiler T, Greenberg CR, Zelinski T, Nylen E, Coghlan G, Crumley MJ, Fujiwara TM, Morgan K, Wrogemann K (1998) A gene for autosomal recessive limb-girdle muscular dystrophy in Manitoba Hutterites maps to chromosome region 9q31–q33: evidence for another limb-girdle muscular dystrophy locus. Am J Hum Genet 63:140–147

    Article  PubMed  CAS  Google Scholar 

  85. Windpassinger C, Schoser B, Straub V, Hochmeister S, Noor A, Lohberger B, Farra N, Petek E, Schwarzbraun T, Ofner L, Loscher WN, Wagner K, Lochmuller H, Vincent JB, Quasthoff S (2008) An X-linked myopathy with postural muscle atrophy and generalized hypertrophy, termed XMPMA, is caused by mutations in FHL1. Am J Hum Genet 82:88–99

    Article  PubMed  CAS  Google Scholar 

  86. Wong-Kisiel LC, Kuntz NL (2010) Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacort. Neuromuscul Disord 20:122–124

    Article  PubMed  Google Scholar 

  87. Zhang Q, Bethmann C, Worth NF, Davies JD, Wasner C, Feuer A, Ragnauth CD, Yi Q, Mellad JA, Warren DT, Wheeler MA, Ellis JA, Skepper JN, Vorgerd M, Schlotter-Weigel B, Weissberg PL, Roberts RG, Wehnert M, Shanahan CM (2007) Nesprin-1 and -2 are involved in the pathogenesis of Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity. Hum Mol Genet 16:2816–2833

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The financial support of the National Commissioning Group of UK to the Dubowitz Centre for Congenital Muscular Dystrophies and Congenital Myopathies is gratefully acknowledged. In addition I am grateful to many colleagues, especially Professor Francesco Muntoni, Dr Sue Brown, Dr Cecilia Jimenez-Mallebrera and Dr Lucy Feng.

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  1. Dubowitz Neuromuscular Centre, Institute of Child Health, Great Ormond Street Hospital, 30 Guilford Street, London, WC1N 1EH, UK

    Caroline A. Sewry

  2. Wolfson Centre for Inherited Neuromuscular Diseases, RJAH Orthopaedic Hospital, Oswestry, SY10 7AG, UK

    Caroline A. Sewry

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  1. Caroline A. Sewry
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Correspondence to Caroline A. Sewry.

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Sewry, C.A. Muscular dystrophies: an update on pathology and diagnosis. Acta Neuropathol 120, 343–358 (2010). https://doi.org/10.1007/s00401-010-0727-5

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  • DOI: https://doi.org/10.1007/s00401-010-0727-5

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