Intermediate Filament Diseases: Desminopathy

  • Lev G. Goldfarb
  • Montse Olivé
  • Patrick Vicart
  • Hans H. Goebel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 642)


Desminopathy is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins, desmin and alphaB-crystallin. The inheritance pattern in familial desminopathy is characterized as autosomal dominant or autosomal recessive, but many cases have no family history. At least some and likely most sporadic desminopathy cases are associated with de novo DES mutations. The age of disease onset and rate of progression may vary depending on the type of inheritance and location of the causative mutation. Typically, the illness presents with lower and later upper limb muscle weakness slowly spreading to involve truncal, neck-flexor, facial and bulbar muscles. Skeletal myopathy is often combined with cardiomyopathy manifested by conduction blocks, arrhythmias and chronic heart failure resulting in premature sudden death. Respiratory muscle weakness is a major complication in some patients. Sections of the affected skeletal and cardiac muscles show abnormal fibre areas containing chimeric aggregates consisting of desmin and other cytoskeletal proteins. Various DES gene mutations: point mutations, an insertion, small in-frame deletions and a larger exon-skipping deletion, have been identified in desminopathy patients. The majority of these mutations are located in conserved alpha-helical segments, but additional mutations have recently been identified in the tail domain. Filament and network assembly studies indicate that most but not all disease-causing mutations make desmin assembly-incompetent and able to disrupt a pre-existing filamentous network in dominant-negative fashion. AlphaB-crystallin serves as a chaperone for desmin preventing its aggregation under various forms of stress; mutant CRYAB causes cardiac and skeletal myopathies identical to those resulting from DES mutations.


Autosomal Recessive Tail Domain Skeletal Myopathy Skeletal Muscle Disease Skeletal Muscle Pathology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Goebel HH, Voit T, Warlo I et al. Immunohistologic and electron microscopic abnormalities of desmin and dystrophin in familial cardiomyopathy and myopathy. Rev Neurol (Paris) 1994; 150:452–459.Google Scholar
  2. 2.
    Selcen D, Ohno K, Engel AG. Myofibrillar myopathy: Clinical, morphological and genetic studies in 63 patients. Brain 2004; 127:439–451.PubMedCrossRefGoogle Scholar
  3. 3.
    Park KY, Dalakas MC, Goebel HH et al. Desmin splice variants causing cardiac and skeletal myopathy. J Med Genet 2000; 37:851–857.PubMedCrossRefGoogle Scholar
  4. 4.
    Goudeau B, Dagvadorj A, Rodrigues-Lima F et al. Structural and functional analysis of a new desmin variant causing desmin-related myopathy. Hum Mutation 2001; 18:388–396.CrossRefGoogle Scholar
  5. 5.
    Bar H, Strelkov SV, Sjoberg G et al. The biology of desmin filaments: How do mutations affect their structure, assembly and organization. J Struct Biol 2004; 148:137–152.PubMedCrossRefGoogle Scholar
  6. 6.
    Sjoberg G, Saavedra-Matiz CA, Rosen DR et al. Missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy and exerts a dominant negative effect on filament formation. Hum Mol Genet 1999; 8:2191–2198.PubMedCrossRefGoogle Scholar
  7. 7.
    Wang X, Osinska H, Dorn GW II et al. Mouse model of desmin-related cardiomyopathy. Circulation 2001; 103:2402–2407.PubMedGoogle Scholar
  8. 8.
    Vicart P, Caron A, Guicheney P et al. A missense mutation in the alpha-B-crystallin chaperone gene causes a desmin-related myopathy. Nat Genet 1998; 20:92–95.PubMedCrossRefGoogle Scholar
  9. 9.
    Goldfarb LG, Park KY, Cervenakova L et al. Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat Genet 1998; 19:402–403.PubMedCrossRefGoogle Scholar
  10. 10.
    Muñoz-Mármol AM, Strasser G, Isamat M et al. A dysfunctional desmin mutation in a patient with severe generalized myopathy. Proc Nat Acad Sci 1998; 95:11312–11317.PubMedCrossRefGoogle Scholar
  11. 11.
    Dalakas MC, Park K-Y, Semino-Mora C et al. Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. N Engl J Med 2000; 342:770–780.PubMedCrossRefGoogle Scholar
  12. 12.
    Wang X, Osinska H, Klevitsky R et al. Expression of R120G—aB-crystallin causes aberrant desmin and aB-crystallin aggregation and cardiomyopathy in mice. Circ Res 2001; 89:84–91.PubMedCrossRefGoogle Scholar
  13. 13.
    Wilhelmsen KC, Blake DM, Lynch T et al. Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy. Ann Neurol 1996; 39:507–520.PubMedCrossRefGoogle Scholar
  14. 14.
    Melberg A, Oldfors A, Blomstrom-Lundqvist C et al. Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q. Ann Neurol 1999; 46:684–692.CrossRefGoogle Scholar
  15. 15.
    Selcen D, Engel AG. Myofibrillar myopathy. GeneReviews ( 2006.Google Scholar
  16. 16.
    Fuchs E, Weber K. Intermediate filaments: Structure, dynamics, function and disease. Annu Rev Biochem 1994; 63:345–382.PubMedGoogle Scholar
  17. 17.
    Herrmann H, Aebi U. Intermediate filaments: Molecular structure, assembly mechanism and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem 2004; 73:749–789.PubMedCrossRefGoogle Scholar
  18. 18.
    Lazarides E. Intermediate filaments as mechanical integrators of cellular space. Nature 1980; 238:249–256.CrossRefGoogle Scholar
  19. 19.
    Schroder R, Furst DO, Klasen C et al. Association of plectin with Z-discs is a prerequisite for the formation of the intermyofibrillar desmin cytoskeleton. Lab Invest 2000; 80:455–464.PubMedGoogle Scholar
  20. 20.
    Price MG. Molecular analysis of intermediate filament cytoskeleton—Putative load-bearing structure. Am J Physiol 1984; 246:566–572.Google Scholar
  21. 21.
    Li Z, Colucci-Guyon E, Pinçon-Raymond M et al. Cardiovascular lesions and skeletal myopathy in mice lacking desmin. Dev Biol 1996; 175:362–366.PubMedCrossRefGoogle Scholar
  22. 22.
    Capetanaki Y, Milner DJ, Weitzer G. Desmin in muscle formation and maintenance: Knockouts and consequences. Cell Struct Funct 1997; 22:103–116.PubMedCrossRefGoogle Scholar
  23. 23.
    Milner DJ, Weitzer G, Tran D et al. Disruption of muscle architecture and myocardial degeneration in mice lacking desmin. J Cell Biol 1996; 134:1255–1270.PubMedCrossRefGoogle Scholar
  24. 24.
    Golenhofen N, Arbeiter A, Koob R et al. Ischemia-induced association of the stress protein alpha B-crystallin with I-band portion of cardiac titin. J Mol Cell Cardiol 2002; 34:309–319.PubMedCrossRefGoogle Scholar
  25. 25.
    Bullard B, Ferguson C, Minajeva A et al. Association of the chaperone alphaB-crystallin with titin in heart muscle. J Biol Chem 2004; 279:7917–7924.PubMedCrossRefGoogle Scholar
  26. 26.
    Inagaki N, Hayashi T, Arimura T. Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem Biophys Res Commun 2006; 342:379–386.PubMedCrossRefGoogle Scholar
  27. 27.
    Viegas-Péquignot E, Li Z, Dutrillaux B et al. Assignment of human desmin gene to band 2q35 by nonradioactive in situ hybridization. Hum Genet 1989; 83:33–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Li Z, Lilienbaum A, Butler-Browne G et al. Human desmin-coding gene: Complete nucleotide sequence, characterization and regulation of expression during myogenesis and development. Gene 1989; 78:243–254.PubMedCrossRefGoogle Scholar
  29. 29.
    Weber K, Geisler N. Intermediate filaments: Structural conservation and divergence. Ann NY Acad Sci 1985; 455:126–143.PubMedCrossRefGoogle Scholar
  30. 30.
    Brown JH, Cohen C, Parry DAD. Heptad breaks in \( \tilde \alpha \)helical coiled coils: Stutters and stammers. Proteins 1996; 26:134–145.PubMedCrossRefGoogle Scholar
  31. 31.
    Strelkov SV, Herrmann H, Geisler N et al. Conserved segments 1A and 2B of the intermediate filament dimer: their atomic structures and role in filament assembly. EMBO J 2002; 21:1255–1266.PubMedCrossRefGoogle Scholar
  32. 32.
    Strelkov SV, Burkhard P. Analysis of \( \tilde \alpha \)helical coiled coils with the program TWISTER reveals a structural mechanism for stutter compensation. J Struct Biol 2002; 137:54–64.PubMedCrossRefGoogle Scholar
  33. 33.
    Herrmann H, Strelkov SV, Feja B et al. The intermediate filament protein consensus motif of helix 2B: Its atomic structure and contribution to assembly. J Mol Biol 2000; 298:817–832.PubMedCrossRefGoogle Scholar
  34. 34.
    Herrmann H, Haner M, Brettel M et al. Structure and assembly properties of the intermediate filament protein vimentin: The role of its head, rod and tail domains. J Mol Biol 1996; 264:933–953.PubMedCrossRefGoogle Scholar
  35. 35.
    Heimburg T, Schuenemann J, Weber K et al. Specific recognition of coiled coils by infrared spectroscopy: analysis of the three structural domains of type III intermediate filament proteins. Biochemistry 1996; 35:1375–1382.PubMedCrossRefGoogle Scholar
  36. 36.
    Rogers KR, Eckelt A, Nimmrich V et al. Truncation mutagenesis of the non-alpha-helical carboxyterminal tail domain of vimentin reveals contributions to cellular localization but not to filament assembly. Eur J Cell Biol 1995; 66:136–150.PubMedGoogle Scholar
  37. 37.
    Arbustini E, Pasotti M, Pilotto A et al. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects. Eur J Heart Fail 2006; 8:477–483.PubMedCrossRefGoogle Scholar
  38. 38.
    Taylor MRG, Slavov D, Ku L et al. Prevalence of desmin mutations in dilated cardiomyopathy. Circulation 2007; 115:1244–1251.PubMedCrossRefGoogle Scholar
  39. 39.
    Bowles NE, Jimenez S, Vatta M et al. Familial restrictive cardiomyopathy caused by a missense mutation in the desmin gene. Pediatric Res 2002; 51:Suppl, p 2, abstract #1304.Google Scholar
  40. 40.
    Goudeau B, Rodrigues-Lima F, Fischer D et al. Variable pathogenic potentials of mutations located in the desmin alpha-helical domain. Hum Mutat 2006; 27:906–913.PubMedCrossRefGoogle Scholar
  41. 41.
    Bushby et al. Genotype-morphotype correlations in myofibrillar myopathies. In preparation.Google Scholar
  42. 42.
    Schröder R, Goudeau B, Casteras-Simon M et al. On noxious desmin: Functional effects of a novel heterozygous desmin insertion mutation on the extrasarcomeric desmin cytoskeleton and mitochondria. Hum Mol Genet 2003; 12:657–669.PubMedCrossRefGoogle Scholar
  43. 43.
    Vrabie A, Goldfarb LG, Shatunov A et al. The enlarging spectrum of desminopathies: New morphological findings, eastward geographic spread, novel exon 3 desmin mutation. Acta Neuropathol (Berl) 2005; 109:411–417.CrossRefGoogle Scholar
  44. 44.
    Shatunov A, Dalakas MC, Park K-Y et al. Desmin splice variants causing cardiac and skeletal myopathy. Amer J Hum Genet 2003; 73: Suppl, Abstract.Google Scholar
  45. 45.
    Yuri T, Miki K, Tsukamoto R et al. Autopsy case of desminopathy involving skeletal and cardiac muscle. Pathol Int 2007; 57:32–36.PubMedCrossRefGoogle Scholar
  46. 46.
    Bar H, Fischer D, Goudeau B et al. Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro. Hum Mol Gen 2005; 14:1251–1260.PubMedCrossRefGoogle Scholar
  47. 47.
    Fidzianska A, Kotowicz J, Sadowska M et al. A novel desmin R355P mutation causes cardiac and skeletal myopathy. Neuromuscul Disord 2005; 15:525–531.PubMedCrossRefGoogle Scholar
  48. 48.
    Dagvadorj A, Goudeau B, Hilton-Jones D et al. Respiratory insufficiency in desminopathy patients caused by introduction of proline residues in desmin C-terminal α-helical segment. Muscle Nerve 2003; 27:669–675.PubMedCrossRefGoogle Scholar
  49. 49.
    Kaminska A, Strelkov SV, Goudeau B et al. Small deletions disturb desmin architecture leading to breakdown of muscle cells and development of skeletal or cardioskeletal myopathy. Hum Genet 2004; 114:306–313.PubMedCrossRefGoogle Scholar
  50. 50.
    Olivé M, Armstrong J, Miralles F et al. Phenotypic patterns of desminopathy associated with three novel mutations in the desmin gene. Neuromuscul Disord 2007; 17:443–450.PubMedCrossRefGoogle Scholar
  51. 51.
    Arias M, Pardo J, Blanco-Arias P et al. Distinct phenotypic features and gender-specific disease manifestations in a spanish family with desmin L370P mutation. Neuromuscul Disord 2006; 16:498–503.PubMedCrossRefGoogle Scholar
  52. 52.
    Sugawara M, Kato K, Komatsu M et al. A novel de novo mutation in the desmin gene causes desmin myopathy with toxic aggregates. Neurology 2000; 55:986–990.PubMedGoogle Scholar
  53. 53.
    Goudeau B, Dagvadorj A, Rodrigues-Lima F et al. Structural and functional analysis of a new desmin variant causing desmin-related myopathy. Hum Mutat 2001; 18:388–396.PubMedCrossRefGoogle Scholar
  54. 54.
    Dagvadorj A, Olivé M, Urtizberea J-A et al. West European cluster of patients with severe cardioskeletal myopathy associated with a de novo R406W mutation in desmin. J Neurol 2004, 251:143–149.PubMedCrossRefGoogle Scholar
  55. 55.
    Pruszczyk P, Kostera-Pruszczyk A, Shatunov A et al. Restrictive cardiomyopathy with atrioventricular conduction block resulting from a desmin mutation. Int J Cardiol 2006; 117:244–253.PubMedCrossRefGoogle Scholar
  56. 56.
    Bar H, Goudeau B, Walde S et al. Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies. Human Mut 2007; 28:374–386.CrossRefGoogle Scholar
  57. 57.
    Li D, Tapscoft T, Gonzalez O et al. Desmin mutation responsible for idiopathic dilated cardiomyopathy. Circulation 1999; 100:461–464.PubMedGoogle Scholar
  58. 58.
    Dalakas MC, Dagvadorj A, Goudeau B et al. Progressive skeletal myopathy, a phenotypic variant of desmin myopathy associated with desmin mutations. Neuromusc Disord 2003; 13:252–258.PubMedCrossRefGoogle Scholar
  59. 59.
    Miyamoto Y, Akita H, Shiga N et al. Frequency and clinical characteristics of dilated cardiomyopathy caused by desmin gene mutation in a Japanese population. Eur Heart J 2001; 22:2284–2289.PubMedCrossRefGoogle Scholar
  60. 60.
    Muntoni F, Bonne G, Goldfarb LG et al. Disease severity in dominant Emery Dreifuss is increased by mutations in both emerin and desmin proteins. Brain 2006; 129:1260–1268.PubMedCrossRefGoogle Scholar
  61. 61.
    Bar H, Mucke N, Kostareva A et al. Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages. Proc Natl Acad Sci USA. 2005;102:15099–15104.PubMedCrossRefGoogle Scholar
  62. 62.
    Bang ML, Gregorio C, Labeit S. Molecular dissection of the interaction of desmin with the C-terminal region of nebulin. J Struct Biol 2002; 137:119–127.PubMedCrossRefGoogle Scholar
  63. 63.
    MacArthur MW, Thornton JM. Influence of proline residues on protein conformation. J Mol Biol 1991; 218:397–412.PubMedCrossRefGoogle Scholar
  64. 64.
    Raats JMH, Henderik JBJ, Verdijk M et al. Assembly of carboxy-terminally deleted desmin in vimentin-free cells. Eur J Cell Biol 1991; 56:84–103.PubMedGoogle Scholar
  65. 65.
    Brakenhoff RH, Guerts van Kessel AH et al. Human alpha B-crystallin (CRYA2) gene mapped to chromosome 11q12-q23. Hum Genet 1990; 85:237–240.PubMedCrossRefGoogle Scholar
  66. 66.
    Dubin RA, Ally AH, Chung S et al. Human alpha-B-crystallin gene and preferential promoter function in lens. Genomics 1990; 7:594–601.PubMedCrossRefGoogle Scholar
  67. 67.
    Horwitz J. The function of alpha-crystallin in vision. Semin Cell Dev Biol 2000; 11:53–60.PubMedCrossRefGoogle Scholar
  68. 68.
    Golenhofen N, Htun P, Ness W et al. Binding of the stress protein alpha B-crystallin to cardiac myofibrils correlates with the degree of myocardial damage during ischemia/reperfusion in vivo. J Mol Cell Cardiol 1999; 31:569–580.PubMedCrossRefGoogle Scholar
  69. 69.
    Martin JL, Mestril R, Hilal-Dandan R et al. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation 1997; 96:4343–4348.PubMedGoogle Scholar
  70. 70.
    Hahner A, Erdmann J, Kallisch H et al. Five novel genetic variants in the promoter and coding region of the alphaB-crystallin gene (CRYAB): −652G>A, −650C>G, −249G>C, S41Y, P51L. Hum Mutat 2000; 16:374–377.PubMedCrossRefGoogle Scholar
  71. 71.
    Fardeau M, Godet-Guillain J, Tome FM et al. Une nouvelle affection musculaire familiale, definie par l’accumulation intra-sarco-plasmique d’un materiel granulo-filamentaire dense en microscopie electronique. Rev Neurol 1978; 134:411–425.PubMedGoogle Scholar
  72. 72.
    Bova MP, Yaron O, Huang Q et al. Mutation R120G in aB-crystallin, which is linked to a desmin-related myopathy, results in an irregular structure and defective chaperone-like function. Proc Natl Acad Sci USA 1999; 96:6137–6142.PubMedCrossRefGoogle Scholar
  73. 73.
    Chavez Zobel AT, Loranger A, Marceau N et al. Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alpha-B-crystallin mutant. Hum Molec Genet 2003; 12:1609–1620.PubMedCrossRefGoogle Scholar
  74. 74.
    Fu L, Liang JJ-N. Alteration of protein-protein interactions of congenital cataract crystallin mutants. Invest Ophthal Vis Sci 2003; 44:1155–1159.PubMedCrossRefGoogle Scholar
  75. 75.
    Selcen D, Engel AG. Myofibrillar myopathy caused by novel dominant negative alpha-B-crystallin mutations. Ann Neurol 2003; 54:804–810.PubMedCrossRefGoogle Scholar
  76. 76.
    Berry V, Francis P, Reddy MA et al. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am J Hum Genet 2001; 69:1141–1145.PubMedCrossRefGoogle Scholar
  77. 77.
    Liu M, Ke T, Wang Z et al. Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family. Invest Ophthalmol Vis Sci 2006; 47:3461–3466.PubMedCrossRefGoogle Scholar
  78. 78.
    Nakano S, Engel AG, Waclawik AJ et al. Myofibrillar myopathy with abnormal foci of desmin positivity. Light and electron microscopy analysis of 10 cases. J Neuropathol Exp Neurol 1996; 55:549–562.PubMedCrossRefGoogle Scholar
  79. 79.
    Bar H, Kostareva A, Sjoberg G et al. Forced expression of desmin and desmin mutants in cultured cells: Impact of myopathic missense mutations in the central coiled-coil domain on network formation. Exp Cell Res 2006; 312:1554–1565.PubMedCrossRefGoogle Scholar
  80. 80.
    Herrmann H, Aebi U. Intermediate filaments: Molecular structure, assembly mechanism and integration into functionally distinct intracellular scaffolds. Annu Rev Biochem 2004; 73:749–789.PubMedCrossRefGoogle Scholar
  81. 81.
    Thornell L-E, Carlsson L, Mericskay M et al. Null mutation in the desmin gene gives rise to a cardiomyopathy. J Moll Cell Cardiol 1997; 29:2107–2124.CrossRefGoogle Scholar
  82. 82.
    Li M, Dalakas MC. Abnormal desmin protein in myofibrillar myopathies caused by desmin gene mutations. Desmin protein in myofibrillar myopathies. Ann Neurol 2001; 49:532–536.PubMedCrossRefGoogle Scholar
  83. 83.
    Bar H, Mucke N, Ringler P et al. Impact of disease mutations on the desmin filament assembly process. J Mol Biol 2006; 360:1031–1042.PubMedCrossRefGoogle Scholar
  84. 84.
    Raats JM, Schaart G, Henderik JB et al. Muscle-specific expression of a dominant negative desmin mutant in transgenic mice. Eur J Cell Biol 1996; 71:221–236.PubMedGoogle Scholar
  85. 85.
    Carlsson L, Fischer C, Sjoberg G et al. Cytoskeletal derangements in hereditary myopathy with a desmin L345P mutation. Acta Neuropathol 2002; 104:493–504.PubMedGoogle Scholar
  86. 86.
    Agbulut O, Li Z, Mouly V et al. Analysis of skeletal and cardiac muscle from desmin knock-out and normal mice by high resolution separation of myosin heavy-chain isoforms. Biol Cell 1996; 88:131–135.PubMedCrossRefGoogle Scholar
  87. 87.
    Paulin D, Huet A, Khanamyrian L et al. Desminopathies in muscle disease. J Pathol 2004; 204:418–427.PubMedCrossRefGoogle Scholar
  88. 88.
    Yu KR, Hijikata T, Lin ZX et al. Truncated desmin in PtK2 cells induces desmin-vimentin-cytokeratin coprecipitation, involution of intermediate filament networks and nuclear fragmentation: A model for many degenerative diseases. Proc Natl Acad Sci USA 1994; 91:2497–2501.PubMedCrossRefGoogle Scholar
  89. 89.
    Perng MD, Muchowski PJ, van den Ijssel P et al. The cardiomyopathy and lens cataract mutation in alpha B-crystallin alters its protein structure, chaperone activity and interaction with intermediate filaments in vitro. J Biol Chem 1999, 274:33235–33243.PubMedCrossRefGoogle Scholar
  90. 90.
    Wang X, Osinska H, Gerdes AM et al. Desmin filaments and cardiac disease: Establishing causality. J Cardiac Failure 2002; 8:S287–S292.CrossRefGoogle Scholar
  91. 91.
    Sanbe A, Osinska H, Saffitz JE et al. Desmin-related cardiomyopathy in transgenic mice: A cardiac amyloidosis. Proc Natl Acad Sci USA 2004; 101:10132–10136.PubMedCrossRefGoogle Scholar
  92. 92.
    Sanbe A, Osinska H, Villa C et al. Reversal of amyloid-induced heart disease in desmin-related cardiomyopathy. Proc Natl Acad Sci USA 2005; 102:13592–13597.PubMedCrossRefGoogle Scholar
  93. 93.
    Nakano S, Engel AG, Akiguchi I et al. Myofibrillar myopathy. III. Abnormal expression of cyclindependent kinases and nuclear proteins. J Neuropathol Exp Neurol 1997; 56:850–856.PubMedCrossRefGoogle Scholar
  94. 94.
    Caron A, Chapon F. Desmin phosphorylation abnormalities in cytoplasmic body and desmin-related myopathies. Muscle Nerve 1999; 22:1122–1125.PubMedCrossRefGoogle Scholar
  95. 95.
    Rappaport L, Contard F, Samuel JL et al. Storage of phosphorylated desmin in a familial myopathy. FEBS Lett 1988; 231:421–415.PubMedCrossRefGoogle Scholar
  96. 96.
    Dalakas MC, Vasconcelos OM, Kaminska A et al. Desmin myopathy: Distinct filamentopathy caused by mutations in the desmin gene. Acta Myologica 2002; 21:138–143.Google Scholar
  97. 97.
    Olivé M, Goldfarb L, Moreno D et al. Desmin-related myopathy: Clinical, electrophysiological, radiological, neuropathological and genetic studies. J Neurol Sci 2004; 219:125–137.PubMedCrossRefGoogle Scholar
  98. 98.
    Boriek AM, Capetanaki Y, Hwang W et al. Desmin integrates the three-dimensional mechanical properties of muscles. Am J Physiol Cell Physiol 2001; 280:C46–C52.PubMedGoogle Scholar
  99. 99.
    Towbin JA, Bowles NE. The failing heart. Nature 2002; 415:227–233.PubMedCrossRefGoogle Scholar
  100. 100.
    Takeda N. Cardiomyopathy: Molecular and immunological aspects (review). Int J Mol Med 2003; 11:13–16.PubMedGoogle Scholar
  101. 101.
    Horowitz SH, Schmalbruch H. Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship. Muscle Nerve 1994; 17:151–160.PubMedCrossRefGoogle Scholar
  102. 102.
    Ariza A, Coll J, Fernandez-Figueras MT et al. Desmin myopathy: A multisystem disorder involving skeletal, cardiac and smooth muscle. Hum Pathol 1995; 26:1032–1037.PubMedCrossRefGoogle Scholar
  103. 103.
    Fardeau M, Vicart P, Caron A et al. Myopathie familiale avec surcharge en desmine, sous forme de matériel granulo-filamentaire dense en microscopie électronique, avec mutation dans le gène de l’alpha-B-cristalline. Rev Neurol (Paris) 2000; 156:497–504.Google Scholar
  104. 104.
    Goebel HH. Desmin-related neuromuscular disorders. Muscle Nerve 1995; 18:1306–1320.PubMedCrossRefGoogle Scholar
  105. 105.
    Sarnat HB. Vimentin and desmin in maturing skeletal muscle and developmental myopathies. Neurology 1992; 42:1616–1624.PubMedGoogle Scholar
  106. 106.
    Thornell LE, Edstrom L, Eriksson A et al. The distribution of intermediate filament protein (skeletin) in normal and diseased human skeletal muscle—An immunohistochemical and electron-microscopic study. J Neurol Sci 1980; 47:153–170.PubMedCrossRefGoogle Scholar
  107. 107.
    Askanas V, Bornemann A, Engel WK. Immunocytochemical localization of desmin at human neuromuscular junction. Neurology 1990; 40:949–953.PubMedGoogle Scholar
  108. 108.
    Tidball JC. Desmin at myotendinous junctions. Exp Cell Res 1992; 199:341–348.PubMedCrossRefGoogle Scholar
  109. 109.
    Howman EV, Sullivan N, Poon EP et al. Syncoilin accumulation in two patients with desmin-related myopathy. Neuromuscul Disord 2003; 13:42–48.PubMedCrossRefGoogle Scholar
  110. 110.
    Engel AG. Myofibrillar myopathy. Ann Neurol 1999; 46:681–683.PubMedCrossRefGoogle Scholar
  111. 111.
    Selcen D, Engel AG. Mutations in myotilin cause myofibrillar myopathy. Neurology 2004; 62:1363–1371.PubMedGoogle Scholar
  112. 112.
    Olivé M, Goldfarb LG, Shatunov A et al. Myotilinopathy: Refining the clinical and myopathological phenotype. Brain 2005; 128: 2315–2326.PubMedCrossRefGoogle Scholar
  113. 113.
    Olivé M, van Leeuwen Fred W, Janué A et al. Expression of mutant ubiquitin (UBB+1) and p62 in myotilinopathies and desminopathies. Neuropathol Appl Neurobiol 2007, in press.Google Scholar
  114. 114.
    Fischer D, Clamen CS, Olivé M et al. Different early patogenesis in myotilinopathy compared to primary desminopathy. Neuromuscul Disord 2006; 16:361–367.PubMedCrossRefGoogle Scholar
  115. 115.
    Selcen D, Engel AG. Mutations in ZASP define a novel form of muscular dystrophy in humans. Ann Neurol 2005; 57:269–276.PubMedCrossRefGoogle Scholar
  116. 116.
    Penisson-Besnier I, Talvinen K, Dumez C et al. Myotilinopathy in a family with late onset myopathy. Neuromuscul Disord 2006; 16:427–431.PubMedCrossRefGoogle Scholar
  117. 117.
    Ferreiro A, Ceuterick-de Groote C et al. Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. Ann Neurol 2004; 55:676–686.PubMedCrossRefGoogle Scholar
  118. 118.
    Vorgerd M, van der Ven PF, Bruchertseifer V et al. A mutation in the dimerization domain of filamin C causes a novel type of autosomal dominant myofibrillar myopathy. Am J Hum Genet 2005; 77:297–304.PubMedCrossRefGoogle Scholar
  119. 119.
    Hübbers CU, Clemen CS, Kesper K et al. Pathological consequences of VCP mutations on human striated muscle. Brain 2007; 130:381–393.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Lev G. Goldfarb
    • 1
  • Montse Olivé
    • 2
  • Patrick Vicart
    • 3
  • Hans H. Goebel
    • 4
  1. 1.National Institutes of HealthBethesdaUSA
  2. 2.Institut de Neuropatologia IDIBELL-Hospital de BellvitgeHospitalet de LlobregatBarcelonaSpain
  3. 3.Laboratoire Cytosquelette et DéveloppementParisFrance
  4. 4.Department of NeuropathologyMainz University Medical CenterMainzGermany

Personalised recommendations