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Current Neurology and Neuroscience Reports

, Volume 12, Issue 2, pp 165–174 | Cite as

Congenital Myopathies: An Update

  • Jessica R. Nance
  • James J. Dowling
  • Elizabeth M. Gibbs
  • Carsten G. BönnemannEmail author
Pediatric Neurology (R Packer, Section Editor)

Abstract

Congenital myopathy is a clinicopathological concept of characteristic histopathological findings on muscle biopsy in a patient with early-onset weakness. Three main categories are recognized within the classical congenital myopathies: nemaline myopathy, core myopathy, and centronuclear myopathy. Recent evidence of overlapping clinical and histological features between the classical forms and their different genetic entities suggests that there may be shared pathomechanisms between the congenital myopathies. Animal models, especially mouse and zebrafish, have been especially helpful in elucidating such pathomechanisms associated with the congenital myopathies and provide models in which future therapies can be investigated.

Keywords

Congenital myopathy Nemaline rod myopathy Core myopathy Central core disease Multiminicore disease Centronuclear myopathy ACTA1 NEB TMP2 TPM3 TNNT1 Cofilin 2 KTBDB13 RYR1 SEPN1 MTM1 DNM2 BIN1 

Notes

Acknowledgements

CGB’s research is supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, JD is supported by an NIH K08 award (NIH1K08AR054835). We apologize to researchers whose work could not be cited due to this reviews restrictions in length and focus.

Disclosure

No potential conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Gonatas NK. The fine structure of the rod-like bodies in nemaline myopathy and their relation to the Z-discs. J Neuropathol Exp Neurol. 1966;25:409–21.PubMedCrossRefGoogle Scholar
  2. 2.
    Goebel HH, Warlo I. Nemaline myopathy with intranuclear rods–intranuclear rod myopathy. Neuromuscul Disord. 1997;7:13–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Nowak KJ, Wattanasirichaigoon D, Goebel HH, et al. Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy. Nat Genet. 1999;23:208–12.PubMedCrossRefGoogle Scholar
  4. 4.
    Pelin K, Hilpela P, Donner K, et al. Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy. Proc Natl Acad Sci USA. 1999;96:2305–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Laing NG, Wilton SD, Akkari PA, et al. A mutation in the alpha tropomyosin gene TPM3 associated with autosomal dominant nemaline myopathy. Nat Genet. 1995;9:75–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Donner K, Ollikainen M, Ridanpaa M, et al. Mutations in the beta-tropomyosin (TPM2) gene–a rare cause of nemaline myopathy. Neuromuscul Disord. 2002;12:151–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Johnston JJ, Kelley RI, Crawford TO, et al. A novel nemaline myopathy in the Amish caused by a mutation in troponin T1. Am J Hum Genet. 2000;67:814–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Agrawal PB, Greenleaf RS, Tomczak KK, et al. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am J Hum Genet. 2007;80:162–1677.PubMedCrossRefGoogle Scholar
  9. 9.
    •• Sambuughin N, Yau KS, Olive M, et al. Dominant mutations in KBTBD13, a member of the BTB/Kelch family, cause nemaline myopathy with cores. Am J Hum Genet. 2010;87:842–7. This article describes the identification of a new gene associated with NM with both rods and cores, known as NM type 6.PubMedCrossRefGoogle Scholar
  10. 10.
    Ryan MM, Schnell C, Strickland CD, et al. Nemaline myopathy: a clinical study of 143 cases. Ann Neurol. 2001;50:312–20.PubMedCrossRefGoogle Scholar
  11. 11.
    • Laing NG, Dye DE, Wallgren-Pettersson C, et al. Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1). Hum Mutat. 2009;30:1267–77. This established the first large database describing ACTA1 mutations. Evaluation of this data is important for the delineation of emerging genotype-phenotype relationships.PubMedCrossRefGoogle Scholar
  12. 12.
    Wallgren-Pettersson C, Lehtokari VL, Kalimo H, et al. Distal myopathy caused by homozygous missense mutations in the nebulin gene. Brain. 2007;130:1465–76.PubMedCrossRefGoogle Scholar
  13. 13.
    Sung SS, Brassington AM, Grannatt K, et al. Mutations in genes encoding fast-twitch contractile proteins cause distal arthrogryposis syndromes. Am J Hum Genet. 2003;72:681–90.PubMedCrossRefGoogle Scholar
  14. 14.
    Lawlor MW, Ottenheijm CA, Lehtokari VL, et al. Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy. Skelet Muscle 2011;1:23. http://www.skeletalmusclejournal.com/
  15. 15.
    Monnier N, Lunardi J, Marty I, et al. Absence of beta-tropomyosin is a new cause of Escobar syndrome associated with nemaline myopathy. Neuromuscul Disord. 2009;19:118–23.PubMedCrossRefGoogle Scholar
  16. 16.
    Shimomura C, Nonaka I. Nemaline myopathy: comparative muscle histochemistry in the severe neonatal, moderate congenital, and adult-onset forms. Pediatr Neurol. 1989;5:25–31.PubMedCrossRefGoogle Scholar
  17. 17.
    Ilkovski B, Cooper ST, Nowak K, et al. Nemaline myopathy caused by mutations in the muscle alpha-skeletal-actin gene. Am J Hum Genet. 2001;68:1333–43.PubMedCrossRefGoogle Scholar
  18. 18.
    Feng JJ, Marston S. Genotype-phenotype correlations in ACTA1 mutations that cause congenital myopathies. Neuromuscul Disord. 2009;19:6–16.PubMedCrossRefGoogle Scholar
  19. 19.
    Ravenscroft G, Wilmshurst JM, Pillay K, et al. A novel ACTA1 mutation resulting in a severe congenital myopathy with nemaline bodies, intranuclear rods and type I fibre predominance. Neuromuscul Disord. 2011;21:31–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Laing NG, Wallgren-Pettersson C. 161st ENMC International Workshop on nemaline myopathy and related disorders, Newcastle upon Tyne, 2008. Neuromuscul Disord. 2009;19:300–5.PubMedCrossRefGoogle Scholar
  21. 21.
    •• Ravenscroft G, Jackaman C, Bringans S, et al. Mouse models of dominant ACTA1 disease recapitulate human disease and provide insight into therapies. Brain 2011;134:1101–15. This describes the development of two transgenic ACTA1 mouse models, one with severe disease and another with moderate disease, which demonstrate that the severity of ACTA1-related myopathy may be dependent on the amount of mutant protein expressed.PubMedCrossRefGoogle Scholar
  22. 22.
    Nowak KJ, Ravenscroft G, Jackaman C, et al. Rescue of skeletal muscle alpha-actin-null mice by cardiac (fetal) alpha-actin. J Cell Biol. 2009;185:903–15.PubMedCrossRefGoogle Scholar
  23. 23.
    Jaeger MA, Sonnemann KJ, Fitzsimons DP, et al. Context-dependent functional substitution of alpha-skeletal actin by gamma-cytoplasmic actin. FASEB J. 2009;23:2205–14.PubMedCrossRefGoogle Scholar
  24. 24.
    Ryan MM, Sy C, Rudge S, et al. Dietary L-tyrosine supplementation in nemaline myopathy. J Child Neurol. 2008;23:609–13.PubMedCrossRefGoogle Scholar
  25. 25.
    Nguyen MA, Joya JE, Kee AJ, et al. Hypertrophy and dietary tyrosine ameliorate the phenotypes of a mouse model of severe nemaline myopathy. Brain. 2011;134:3513–26.CrossRefGoogle Scholar
  26. 26.
    Jungbluth H, Sewry CA, Counsell S, et al. Magnetic resonance imaging of muscle in nemaline myopathy. Neuromuscul Disord. 2004;14:779–84.PubMedCrossRefGoogle Scholar
  27. 27.
    •• Romero NB, Lehtokari VL, Quijano-Roy S, et al. Core-rod myopathy caused by mutations in the nebulin gene. Neurology 2009;73:1159–61. This is a description of a patient with nebulin-related myopathy with rods and cores, which on muscle biopsy represents a novel association between gene mutation and overlapping histopathological phenotypes.PubMedCrossRefGoogle Scholar
  28. 28.
    Chen MJ, Shih CL, Wang K. Nebulin as an actin zipper. A two-module nebulin fragment promotes actin nucleation and stabilizes actin filaments. J Biol Chem. 1993;268:20327–34.PubMedGoogle Scholar
  29. 29.
    Witt CC, Burkart C, Labeit D, et al. Nebulin regulates thin filament length, contractility, and Z-disk structure in vivo. EMBO J. 2006;25:3843–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Bang ML, Li X, Littlefield R, et al. Nebulin-deficient mice exhibit shorter thin filament lengths and reduced contractile function in skeletal muscle. J Cell Biol. 2006;173:905–16.PubMedCrossRefGoogle Scholar
  31. 31.
    Chandra M, Mamidi R, Ford S, et al. Nebulin alters cross-bridge cycling kinetics and increases thin filament activation: a novel mechanism for increasing tension and reducing tension cost. J Biol Chem. 2009;284:30889–96.PubMedCrossRefGoogle Scholar
  32. 32.
    • Ottenheijm CA, Hooijman P, DeChene ET, et al. Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2). J Struct Biol. 2009;170:334–43. This study of muscle from patients with nebulin-related NM demonstrates that mutation of nebulin alters thin filament length and alters contraction kinetics resulting in decreased force generation.PubMedCrossRefGoogle Scholar
  33. 33.
    Ottenheijm CA, Witt CC, Stienen GJ, et al. Thin filament length dysregulation contributes to muscle weakness in nemaline myopathy patients with nebulin deficiency. Hum Mol Genet. 2009;18:2359–69.PubMedCrossRefGoogle Scholar
  34. 34.
    Telfer WR, Nelson DD, Waugh T, et al: neb: a zebrafish model of nemaline myopathy due to nebulin mutation. Dis Model Mech. 2011, In press.Google Scholar
  35. 35.
    Olive M, Goldfarb LG, Lee HS, et al. Nemaline myopathy type 6: clinical and myopathological features. Muscle Nerve. 2010;42:901–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Monnier N, Romero NB, Lerale J, et al. An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor. Hum Mol Genet. 2000;9:2599–608.PubMedCrossRefGoogle Scholar
  37. 37.
    Scacheri PC, Hoffman EP, Fratkin JD, et al. A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy. Neurology. 2000;55:1689–96.PubMedGoogle Scholar
  38. 38.
    Ono S, Ono K. Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics. J Cell Biol. 2002;156:1065–76.PubMedCrossRefGoogle Scholar
  39. 39.
    Kaindl AM, Ruschendorf F, Krause S, et al. Missense mutations of ACTA1 cause dominant congenital myopathy with cores. J Med Genet. 2004;41:842–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Hernandez-Lain A, Husson I, Monnier N, et al. De novo RYR1 heterozygous mutation (I4898T) causing lethal core-rod myopathy in twins. Eur J Med Genet. 2011;54:29–33.PubMedCrossRefGoogle Scholar
  41. 41.
    Dubowitz V, Pearse AG. Oxidative enzymes and phosphorylase in central-core disease of muscle. Lancet. 1960;2:23–4.PubMedCrossRefGoogle Scholar
  42. 42.
    Dubowitz V, Roy S. Central core disease of muscle: clinical, histochemical and electron microscopic studies of an affected mother and child. Brain. 1970;93:133–46.PubMedCrossRefGoogle Scholar
  43. 43.
    Engel WK, Foster JB, Hughes BP, et al. Central core disease-an investigation of a rare muscle cell abnormality. Brain. 1961;84:167–85.PubMedCrossRefGoogle Scholar
  44. 44.
    Jungbluth H. Central core disease. Orphanet J Rare Dis. 2007;2:25. http://www.ojrd.com/content/.
  45. 45.
    • Amburgey K, McNamara N, Bennett LR, et al. Prevalence of congenital myopathies in a representative pediatric united states population. Ann Neurol. 2011;70:662–5. The study shows a similar prevalence of congenital myopathies in Southwestern Michigan compared to previous studies of patients in Sweden and Northern Ireland. It identifies centronuclear myopathies as the most common identifiable pathological subtype of congenital myopathies.PubMedCrossRefGoogle Scholar
  46. 46.
    Wu S, Ibarra MC, Malicdan MC, et al. Central core disease is due to RYR1 mutations in more than 90% of patients. Brain. 2006;129:1470–80.PubMedCrossRefGoogle Scholar
  47. 47.
    Sewry CA, Muller C, Davis M, et al. The spectrum of pathology in central core disease. Neuromuscul Disord. 2002;12:930–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Gamble JG, Rinsky LA, Lee JH. Orthopaedic aspects of central core disease. J Bone Joint Surg Am. 1988;70:1061–6.PubMedGoogle Scholar
  49. 49.
    Jungbluth H, Dowling JJ, Ferreiro A, et al. 182nd ENMC International Workshop: RYR1-related myopathies, 15-17th April 2011, Naarden, The Netherlands. Neuromuscul Disord. 2012;In press.Google Scholar
  50. 50.
    Sei Y, Sambuughin NN, Davis EJ, et al. Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene. Anesthesiology. 2004;101:824–30.PubMedCrossRefGoogle Scholar
  51. 51.
    Jungbluth H, Muller CR, Halliger-Keller B, et al. Autosomal recessive inheritance of RYR1 mutations in a congenital myopathy with cores. Neurology. 2002;59:284–7.PubMedGoogle Scholar
  52. 52.
    Jungbluth H, Zhou H, Hartley L, et al. Minicore myopathy with ophthalmoplegia caused by mutations in the ryanodine receptor type 1 gene. Neurology. 2005;65:1930–5.PubMedCrossRefGoogle Scholar
  53. 53.
    •• Wilmshurst JM, Lillis S, Zhou H, et al. RYR1 mutations are a common cause of congenital myopathies with central nuclei. Ann Neurol. 2010;68:717–26. This article shows that patients with RYR1 mutations have central nuclei on muscle biopsy especially early in the disease course. When biopsied later in life, many of these patients had developed cores. Overall, this supports that histopathological changes occur on a continuum and that the timing and location of muscle biopsy are important factors in diagnosis.PubMedCrossRefGoogle Scholar
  54. 54.
    Clarke NF, Waddell LB, Cooper ST, et al. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat. 2010;31:E1544–50.PubMedCrossRefGoogle Scholar
  55. 55.
    • Bevilacqua JA, Monnier N, Bitoun M, et al. Recessive RYR1 mutations cause unusual congenital myopathy with prominent nuclear internalization and large areas of myofibrillar disorganization. Neuropathol Appl Neurobiol. 2011;37:271–84. This is a second case series confirming that RYR1 mutations may be associated with central nuclei on muscle biopsy early in the disease course. Later muscle biopsies in some of these patients revealed core-like structures.PubMedCrossRefGoogle Scholar
  56. 56.
    Jungbluth H, Davis MR, Muller C, et al. Magnetic resonance imaging of muscle in congenital myopathies associated with RYR1 mutations. Neuromuscul Disord. 2004;14:785–90.PubMedCrossRefGoogle Scholar
  57. 57.
    Klein A, Jungbluth H, Clement E, et al. Muscle magnetic resonance imaging in congenital myopathies due to ryanodine receptor type 1 gene mutations. Arch Neurol. 2011;68:1171–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Boncompagni S, Rossi AE, Micaroni M, et al. Characterization and temporal development of cores in a mouse model of malignant hyperthermia. Proc Natl Acad Sci USA. 2009;106:21996–2001.PubMedCrossRefGoogle Scholar
  59. 59.
    • Zvaritch E, Kraeva N, Bombardier E, et al. Ca2+ dysregulation in Ryr1(I4895T/wt) mice causes congenital myopathy with progressive formation of minicores, cores, and nemaline rods. Proc Natl Acad Sci USA 2009;106:21813–8. This article demonstrates that histopathological findings of minicores, cores, and rods occur on a continuum in this transgenic mouse model of RYR1-related myopathy.PubMedCrossRefGoogle Scholar
  60. 60.
    Arbogast S, Ferreiro A. Selenoproteins and protection against oxidative stress: selenoprotein N as a novel player at the crossroads of redox signaling and calcium homeostasis. Antioxid Redox Signal. 2009;12:893–904.CrossRefGoogle Scholar
  61. 61.
    Schara U, Kress W, Bonnemann CG, et al. The phenotype and long-term follow-up in 11 patients with juvenile selenoprotein N1-related myopathy. Eur J Paediatr Neurol. 2008;12:224–30.PubMedCrossRefGoogle Scholar
  62. 62.
    Ferreiro A, Ceuterick-de Groote C, Marks JJ, et al. Desmin-related myopathy with Mallory body-like inclusions is caused by mutations of the selenoprotein N gene. Ann Neurol. 2004;55:676–86.PubMedCrossRefGoogle Scholar
  63. 63.
    Scoto M, Cirak S, Mein R, et al. SEPN1-related myopathies: clinical course in a large cohort of patients. Neurology. 2011;76:2073–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Jungbluth H, Wallgren-Pettersson C, Laporte JF. 164th ENMC International workshop: 6th workshop on centronuclear (myotubular) myopathies, 16-18th January 2009, Naarden, The Netherlands. Neuromuscul Disord. 2009;19:721–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Jurynec MJ, Xia R, Mackrill JJ, et al. Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscle. Proc Natl Acad Sci USA. 2008;105:12485–90.PubMedCrossRefGoogle Scholar
  66. 66.
    Rederstorff M, Castets P, Arbogast S, et al. Increased muscle stress-sensitivity induced by selenoprotein N inactivation in mouse: a mammalian model for SEPN1-related myopathy. PLoS One 2011, 6:e23094. http://www.plosone.org/.
  67. 67.
    Laporte J, Hu LJ, Kretz C, et al. A gene mutated in X-linked myotubular myopathy defines a new putative tyrosine phosphatase family conserved in yeast. Nat Genet. 1996;13:175–82.PubMedCrossRefGoogle Scholar
  68. 68.
    Shen D, Wang X, Xu H. Pairing phosphoinositides with calcium ions in endolysosomal dynamics: phosphoinositides control the direction and specificity of membrane trafficking by regulating the activity of calcium channels in the endolysosomes. Bioessays. 2011;33:448–57.PubMedCrossRefGoogle Scholar
  69. 69.
    Herman GE, Kopacz K, Zhao W, et al. Characterization of mutations in fifty North American patients with X-linked myotubular myopathy. Hum Mutat. 2002;19:114–21.PubMedCrossRefGoogle Scholar
  70. 70.
    Biancalana V, Caron O, Gallati S, et al. Characterisation of mutations in 77 patients with X-linked myotubular myopathy, including a family with a very mild phenotype. Hum Genet. 2003;112:135–42.PubMedGoogle Scholar
  71. 71.
    Tsai TC, Horinouchi H, Noguchi S, et al. Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism. Neuromuscul Disord. 2005;15:245–52.PubMedCrossRefGoogle Scholar
  72. 72.
    Jungbluth H, Sewry CA, Buj-Bello A, et al. Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation. Neuromuscul Disord. 2003;13:55–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Kristiansen M, Knudsen GP, Tanner SM, et al. X-inactivation patterns in carriers of X-linked myotubular myopathy. Neuromuscul Disord. 2003;13:468–71.PubMedCrossRefGoogle Scholar
  74. 74.
    Romero NB. Centronuclear myopathies: a widening concept. Neuromuscul Disord. 2010;20:223–8.PubMedCrossRefGoogle Scholar
  75. 75.
    • Bevilacqua JA, Bitoun M, Biancalana V, et al. “Necklace” fibers, a new histological marker of late-onset MTM1-related centronuclear myopathy. Acta Neuropathol. 2009;117:283–91. This article describes a new clinical and pathological phenotype of myotubular myopathy with sporadic, late onset and finding of necklace fibers on biopsy in male and female patients.PubMedCrossRefGoogle Scholar
  76. 76.
    •• Dowling JJ, Vreede AP, Low SE, et al. Loss of myotubularin function results in T-tubule disorganization in zebrafish and human myotubular myopathy. PLoS Genet. 2009;5:e1000372. http://www.plosone.org/. This zebrafish model mimics human disease and shows that myotubularin is essential in establishing the architecture of the T-tubule, thereby causing defective calcium release from the sarcoplasmic and disrupting excitation-contraction coupling. Along with the MTM1 knockout mouse, this represents a useful animal model of myotubular myopathy.
  77. 77.
    Tiret L, Blot S, Kessler JL, et al. The cnm locus, a canine homologue of human autosomal forms of centronuclear myopathy, maps to chromosome 2. Hum Genet. 2003;113:297–306.PubMedCrossRefGoogle Scholar
  78. 78.
    Buj-Bello A, Fougerousse F, Schwab Y, et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis. Hum Mol Genet. 2008;17:2132–43.PubMedCrossRefGoogle Scholar
  79. 79.
    •• Al-Qusairi L, Weiss N, Toussaint A, et al. T-tubule disorganization and defective excitation-contraction coupling in muscle fibers lacking myotubularin lipid phosphatase. Proc Natl Acad Sci USA 2009;106:18763–8. This MTM1 mouse model recapitulates human disease and informs the understanding of the molecular mechanism underlying weakness in myotubular myopathy. Disruption of T-tubule architecture and calcium homeostasis contribute to weakness in myotubular myopathy.PubMedCrossRefGoogle Scholar
  80. 80.
    Lawlor MW, Read BP, Edelstein R, et al. Inhibition of activin receptor type IIB increases strength and lifespan in myotubularin-deficient mice. Am J Pathol. 2011;178:784–93.PubMedCrossRefGoogle Scholar
  81. 81.
    •• Robb SA, Sewry CA, Dowling JJ, et al. Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies. Neuromuscul Disord. 2011;21:379–86. Treatment of the MTM1 knockdown zebrafish with acetylcholinesterase inhibitors improves spontaneous and provoked movement, likely by potentiating calcium release from the SR. Treatment of several patients with pyridostigmine improved function.PubMedCrossRefGoogle Scholar
  82. 82.
    Bitoun M, Maugenre S, Jeannet PY, et al. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. 2005;37:1207–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Durieux AC, Prudhon B, Guicheney P, et al. Dynamin 2 and human diseases. J Mol Med (Berl). 2010;88:339–50.CrossRefGoogle Scholar
  84. 84.
    Bitoun M, Bevilacqua JA, Prudhon B, et al. Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. Ann Neurol. 2007;62:666–70.PubMedCrossRefGoogle Scholar
  85. 85.
    Bitoun M, Bevilacqua JA, Eymard B, et al. A new centronuclear myopathy phenotype due to a novel dynamin 2 mutation. Neurology. 2009;72:93–5.PubMedCrossRefGoogle Scholar
  86. 86.
    Koutsopoulos OS, Koch C, Tosch V, et al. Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot-Marie Tooth peripheral neuropathy. PLoS One 2011;6:e27498. http://www.plosone.org/.
  87. 87.
    Fischer D, Herasse M, Bitoun M, et al. Characterization of the muscle involvement in dynamin 2-related centronuclear myopathy. Brain. 2006;129:1463–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Susman RD, Quijano-Roy S, Yang N, et al. Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy. Neuromuscul Disord. 2010;20:229–37.PubMedCrossRefGoogle Scholar
  89. 89.
    Schessl J, Medne L, Hu Y, et al. MRI in DNM2-related centronuclear myopathy: evidence for highly selective muscle involvement. Neuromuscul Disord. 2007;17:28–32.PubMedCrossRefGoogle Scholar
  90. 90.
    Hanisch F, Muller T, Dietz A, et al. Phenotype variability and histopathological findings in centronuclear myopathy due to DNM2 mutations. J Neurol. 2011;258:1085–90.PubMedCrossRefGoogle Scholar
  91. 91.
    Kenniston JA, Lemmon MA. Dynamin GTPase regulation is altered by PH domain mutations found in centronuclear myopathy patients. EMBO J. 2010;29:3054–67.PubMedCrossRefGoogle Scholar
  92. 92.
    Wang L, Barylko B, Byers C, et al. Dynamin 2 mutants linked to centronuclear myopathies form abnormally stable polymers. J Biol Chem. 2010;285:22753–7.PubMedCrossRefGoogle Scholar
  93. 93.
    Durieux AC, Vignaud A, Prudhon B, et al. A centronuclear myopathy-dynamin 2 mutation impairs skeletal muscle structure and function in mice. Hum Mol Genet. 2010;19:4820–36.PubMedCrossRefGoogle Scholar
  94. 94.
    Cowling BS, Toussaint A, Amoasii L, et al. Increased expression of wild-type or a centronuclear myopathy mutant of dynamin 2 in skeletal muscle of adult mice leads to structural defects and muscle weakness. Am J Pathol. 2011;178:2224–35.PubMedCrossRefGoogle Scholar
  95. 95.
    Takei K, Slepnev VI, Haucke V, et al. Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis. Nat Cell Biol. 1999;1:33–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis. 2008;3:26. http://www.ojrd.com/content/.Google Scholar
  97. 97.
    Lee E, Marcucci M, Daniell L, et al. Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science. 2002;297:1193–6.PubMedCrossRefGoogle Scholar
  98. 98.
    Razzaq A, Robinson IM, McMahon HT, et al. Amphiphysin is necessary for organization of the excitation-contraction coupling machinery of muscles, but not for synaptic vesicle endocytosis in Drosophila. Genes Dev. 2001;15:2967–2979.PubMedCrossRefGoogle Scholar
  99. 99.
    Nicot AS, Toussaint A, Tosch V, et al. Mutations in amphiphysin 2 (BIN1) disrupt interaction with dynamin 2 and cause autosomal recessive centronuclear myopathy. Nat Genet. 2007;39:1134–9.PubMedCrossRefGoogle Scholar
  100. 100.
    •• Toussaint A, Cowling BS, Hnia K, et al. Defects in amphiphysin 2 (BIN1) and triads in several forms of centronuclear myopathies. Acta Neuropathol. 2011;121:253–66. This article demonstrates that all three mutations involved in myopathies with central nuclei have a common mechanism of pathogenicity involving disruption of T-tubule architecture and function.PubMedCrossRefGoogle Scholar
  101. 101.
    North K, Ryan M. Nemaline myopathy. GeneReviews at GeneTests: Medical Genetics Information Resource. http://www.genetests.org. Updated October 21, 2010. Accessed January 16, 2010.
  102. 102.
    Malicdan MC, Nishino I. Central core disease. GeneReviews at GeneTests: Medical Genetics Information Resource. http://www.genetests.org. Updated May 11, 2010. Accessed January 16, 2012.
  103. 103.
    Das S, Dowling J, Pierson C. X-Linked centronuclear myopathy. GeneReviews at GeneTests: Medical Genetics Information Resource. http://www.genetests.org. Updated October 6, 2011 Accessed January 16. 2012.
  104. 104.
    Jungbluth H, Wallgren-Pettersson C, Laporte J. Centronuclear (myotubular) myopathy. Orphanet J Rare Dis. 2008;3:26. http://www.plosone.org/.Google Scholar
  105. 105.
    de Haan A, van der Vliet MR, Gommans IM, et al. Skeletal muscle of mice with a mutation in slow alpha-tropomyosin is weaker at lower lengths. Neuromuscul Disord. 2002;12:952–7.PubMedCrossRefGoogle Scholar
  106. 106.
    Hirata H, Watanabe T, Hatakeyama J, et al. Zebrafish relatively relaxed mutants have a ryanodine receptor defect, show slow swimming and provide a model of multi-minicore disease. Development. 2007;134:2771–81.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • Jessica R. Nance
    • 1
  • James J. Dowling
    • 2
  • Elizabeth M. Gibbs
    • 3
  • Carsten G. Bönnemann
    • 4
    Email author
  1. 1.Department of NeurologyChildren’s National Medical CenterWashingtonUSA
  2. 2.Departments of Pediatrics, Neurology, and NeuroscienceUniversity of Michigan Medical CenterAnn ArborUSA
  3. 3.Departments of Neurology and NeuroscienceUniversity of Michigan Medical CenterAnn ArborUSA
  4. 4.Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke/NIHPorter Neuroscience Research CenterBethesdaUSA

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