Neuromuscular Disorders
Volume 18, Issue 1 , Pages 34-44 , January 2008

Limb–girdle muscular dystrophy: Diagnostic evaluation, frequency and clues to pathogenesis

  • Harriet P. Lo

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • ,
  • Sandra T. Cooper

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
    • ,
  • Frances J. Evesson

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • ,
  • Jane T. Seto

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
    • ,
  • Maria Chiotis

      Affiliations

    • Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
    • ,
  • Valerie Tay

      Affiliations

    • Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
    • ,
  • Alison G. Compton

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • ,
  • Anita G. Cairns

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • ,
  • Alistair Corbett

      Affiliations

    • Concord Repatriation General Hospital, Sydney, Australia
    • ,
  • Daniel G. MacArthur

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
    • ,
  • Nan Yang

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • ,
  • Katrina Reardon

      Affiliations

    • Centre for Clinical Neurosciences and Neurological Research, St. Vincent’s Hospital, Melbourne, Australia
    • ,
  • Kathryn N. North

      Affiliations

    • Institute for Neuromuscular Research, The Children’s Hospital at Westmead, Sydney, Australia
    • Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia
    • Corresponding Author InformationCorresponding author. Address: Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead NSW 2145, Sydney, Australia. Tel.: +61 2 98451906; fax: +61 2 98453389.

Received 23 July 2007 ,Revised 23 July 2007 ,Accepted 17 August 2007.

References 

  1. Beckmann JS, Fardeau M. Limb–girdle muscular dystrophies. In:  Emery AE editors. Neuromuscular Disorders: Clinical and Molecular Genetics. Chichester: J. Wiley; 1998;p. 123–156
  2. Weiler T, Greenberg CR, Zelinski T, et al. 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. 1998;63:140–147
  3. Zatz M, Vainzof M, Passos-Bueno MR. Limb–girdle muscular dystrophy: one gene with different phenotypes, one phenotype with different genes. Curr Opin Neurol. 2000;13:511–517
  4. Daniele N, Richard I, Bartoli M. Ins and outs of therapy in limb girdle muscular dystrophies. Int J Biochem Cell Biol. 2007;39:1608–1624
  5. Bushby KM. Making sense of the limb–girdle muscular dystrophies. Brain. 1999;122(Pt 8):1403–1420
  6. Laval SH, Bushby KM. Limb–girdle muscular dystrophies – from genetics to molecular pathology. Neuropathol Appl Neurobiol. 2004;30:91–105
  7. Bushby KM, Beckmann JS. The 105th ENMC sponsored workshop: pathogenesis in the non-sarcoglycan limb–girdle muscular dystrophies, Naarden, April 12–14, 2002. Neuromuscul Disord 2003;13:80–90.
  8. Petrof BJ, Shrager JB, Stedman HH, Kelly AM, Sweeney HL. Dystrophin protects the sarcolemma from stresses developed during muscle contraction. Proc Natl Acad Sci USA. 1993;90:3710–3714
  9. Matsumura K, Ohlendieck K, Ionasescu VV, et al. The role of the dystrophin–glycoprotein complex in the molecular pathogenesis of muscular dystrophies. Neuromuscul Disord. 1993;3:533–535
  10. Richard I, Broux O, Allamand V, et al. Mutations in the proteolytic enzyme calpain 3 cause limb–girdle muscular dystrophy type 2A. Cell. 1995;81:27–40
  11. McNally EM, de Sa Moreira E, Duggan DJ, et al. Caveolin-3 in muscular dystrophy. Hum Mol Genet. 1998;7:871–877
  12. Minetti C, Sotgia F, Bruno C, et al. Mutations in the caveolin-3 gene cause autosomal dominant limb–girdle muscular dystrophy. Nat Genet. 1998;18:365–368
  13. Muchir A, Bonne G, van der Kooi AJ, et al. Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B). Hum Mol Genet. 2000;9:1453–1459
  14. Bione S, Maestrini E, Rivella S, et al. Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy. Nat Genet. 1994;8:323–327
  15. Bashir R, Britton S, Strachan T, et al. A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb–girdle muscular dystrophy type 2B. Nat Genet. 1998;20:37–42
  16. Liu J, Aoki M, Illa I, et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet. 1998;20:31–36
  17. Bansal D, Miyake K, Vogel SS, et al. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature. 2003;423:168–172
  18. Lennon NJ, Kho A, Bacskai BJ, Perlmutter SL, Hyman BT, Brown RH. Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem. 2003;278:50466–50473
  19. Cooper ST, Lo HP, North KN. Single section Western blot: improving the molecular diagnosis of the muscular dystrophies. Neurology. 2003;61:93–97
  20. Walter MC, Petersen JA, Stucka R, et al. FKRP (826C>A) frequently causes limb–girdle muscular dystrophy in German patients. J Med Genet. 2004;41:e50
  21. Hauser MA, Horrigan SK, Salmikangas P, et al. Myotilin is mutated in limb girdle muscular dystrophy 1A. Hum Mol Genet. 2000;9:2141–2147
  22. Speer MC, Yamaoka LH, Gilchrist JH, et al. Confirmation of genetic heterogeneity in limb–girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q. Am J Hum Genet. 1992;50:1211–1217
  23. Moreira ES, Wiltshire TJ, Faulkner G, et al. Limb–girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet. 2000;24:163–166
  24. Frosk P, Weiler T, Nylen E, et al. Limb–girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene. Am J Hum Genet. 2002;70:663–672
  25. Hackman P, Vihola A, Haravuori H, et al. Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin. Am J Hum Genet. 2002;71:492–500
  26. Roberts HL, Day B, Lo H, McLean C, North K. Rippling muscle disease. J Clin Neurosci. 2006;13:576–578
  27. Guglieri M, Magri F, Comi GP. Molecular etiopathogenesis of limb girdle muscular and congenital muscular dystrophies: boundaries and contiguities. Clin Chim Acta. 2005;361:54–79
  28. Michele DE, Barresi R, Kanagawa M, et al. Post-translational disruption of dystroglycan–ligand interactions in congenital muscular dystrophies. Nature. 2002;418:417–422
  29. Brown SC, Torelli S, Brockington M, et al. Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD2I muscular dystrophies. Am J Pathol. 2004;164:727–737
  30. de Paula F, Vieira N, Starling A, et al. Asymptomatic carriers for homozygous novel mutations in the FKRP gene: the other end of the spectrum. Eur J Hum Genet. 2003;11:923–930
  31. Mercuri E, Brockington M, Straub V, et al. Phenotypic spectrum associated with mutations in the fukutin-related protein gene. Ann Neurol. 2003;53:537–542
  32. Poppe M, Cree L, Bourke J, et al. The phenotype of limb–girdle muscular dystrophy type 2I. Neurology. 2003;60:1246–1251
  33. Brockington M, Yuva Y, Prandini P, et al. Mutations in the fukutin-related protein gene (FKRP) identify limb girdle muscular dystrophy 2I as a milder allelic variant of congenital muscular dystrophy MDC1C. Hum Mol Genet. 2001;10:2851–2859
  34. Balci B, Uyanik G, Dincer P, et al. An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker–Warburg syndrome (WWS) caused by a mutation in the POMT1 gene. Neuromuscul Disord. 2005;15:271–275
  35. D’Amico A, Tessa A, Bruno C, et al. Expanding the clinical spectrum of POMT1 phenotype. Neurology. 2006;66:1564–1567[discussion 1461]
  36. Godfrey C, Escolar D, Brockington M, et al. Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy. Ann Neurol. 2006;60:603–610
  37. Fanin M, Fulizio L, Nascimbeni AC, et al. Molecular diagnosis in LGMD2A: mutation analysis or protein testing?. Hum Mutat. 2004;24:52–62
  38. Saenz A, Leturcq F, Cobo AM, et al. LGMD2A: genotype–phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain. 2005;128:732–742
  39. Sorimachi H, Toyama-Sorimachi N, Saido TC, et al. Muscle-specific calpain, p94, is degraded by autolysis immediately after translation, resulting in disappearance from muscle. J Biol Chem. 1993;268:10593–10605
  40. Piccolo F, Moore SA, Ford GC, Campbell KP. Intracellular accumulation and reduced sarcolemmal expression of dysferlin in limb–girdle muscular dystrophies. Ann Neurol. 2000;48:902–912
  41. Chrobakova T, Hermanova M, Kroupova I, et al. Mutations in Czech LGMD2A patients revealed by analysis of calpain3 mRNA and their phenotypic outcome. Neuromuscul Disord. 2004;14:659–665
  42. Huang Y, Laval SH, van Remoortere A, et al. AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration. FASEB J. 2007;21:732–742
  43. Hernandez-Deviez DJ, Martin S, Laval SH, et al. Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3. Hum Mol Genet. 2006;15:129–142
  44. Matsuda C, Hayashi YK, Ogawa M, et al. The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal muscle. Hum Mol Genet. 2001;10:1761–1766
  45. Cagliani R, Magri F, Toscano A, et al. Mutation finding in patients with dysferlin deficiency and role of the dysferlin interacting proteins annexin A1 and A2 in muscular dystrophies. Hum Mutat. 2005;26:283
  46. Moore SA, Shilling CJ, Westra S, et al. Limb–girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol. 2006;65:995–1003
  47. Sveen ML, Schwartz M, Vissing J. High prevalence and phenotype–genotype correlations of limb girdle muscular dystrophy type 2I in Denmark. Ann Neurol. 2006;59:808–815
  48. Jones KJ, Kim SS, North KN. Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular dystrophies. J Med Genet. 1998;35:379–386
  49. Vainzof M, Anderson LV, McNally EM, et al. Dysferlin protein analysis in limb–girdle muscular dystrophies. J Mol Neurosci. 2001;17:71–80
  50. Nguyen K, Bassez G, Bernard R, et al. Dysferlin mutations in LGMD2B, Miyoshi myopathy, and atypical dysferlinopathies. Hum Mutat. 2005;26:165
  51. Herrmann R, Straub V, Blank M, et al. Dissociation of the dystroglycan complex in caveolin-3-deficient limb girdle muscular dystrophy. Hum Mol Genet. 2000;9:2335–2340
  52. Carbone I, Bruno C, Sotgia F, et al. Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia. Neurology. 2000;54:1373–1376
  53. Flucher BE, Phillips JL, Powell JA, Andrews SB, Daniels MP. Coordinated development of myofibrils, sarcoplasmic reticulum and transverse tubules in normal and dysgenic mouse skeletal muscle, in vivo and in vitro. Dev Biol. 1992;150:266–280
  54. Bonnemann CG, Wong J, Jones KJ, et al. Primary gamma-sarcoglycanopathy (LGMD 2C): broadening of the mutational spectrum guided by the immunohistochemical profile. Neuromuscul Disord. 2002;12:273–280

PII: S0960-8966(07)00716-X

doi: 10.1016/j.nmd.2007.08.009

Neuromuscular Disorders
Volume 18, Issue 1 , Pages 34-44 , January 2008

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