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Pathology and Diagnosis of Muscular Dystrophies

  • Carmen NavarroEmail author
  • Susana Teijeira
  • Beatriz San Millán
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 652)

Abstract

Limb girdle muscular dystrophies are a heterogeneous group of muscle disorders predominantly affecting the pelvic and shoulder girdles. They have been classified into autosomal recessive and dominant forms, the former being by far the commonest. Genetic analyses have led to the description of 14 recessive forms and 7 dominant. In four of the dominant forms the chromosomal loci have been localised but the gene and the protein have not been yet identified. The genes and proteins in these subgroups are localised over a wide range across the muscle fiber and at the extracellular matrix.

Immunohistochemistry and Western blotting analyses of the proteins involved in the various forms of muscular dystrophies, have permitted a refined pathological approach, necessary to conduct genetic studies and to offer an appropriate genetic counseling. The application of molecular medicine in genetic muscular dystrophies also brings great expectations to the therapeutic management of these patients.

Keywords:

Dystrophin Extracellular matrix Immunohistochemistry Limb Girdle Muscular Dystrophies Molecular genetics 

References

  1. 1.
    Becker PE, Kiener F. Eine neue X-chromosomale muskeldystrophie. Arch Psychiat-Z Neurol 1955; 193: 427–448.CrossRefGoogle Scholar
  2. 2.
    Beckmann JS, Brown RH, Muntoni F, Urtizberea A, Bonnemann C, Bushby KM. 66th/67th ENMC sponsored international workshop: The limb-girdle muscular dystrophies, 26-28 March 1999, Naarden, The Netherlands. Neuromuscul Disord 1999; 9: 436–445.CrossRefPubMedGoogle Scholar
  3. 3.
    Ben Hamida M, Fardeau M, Attia N. Severe childhood muscular dystrophy affecting both sexes and frequent in Tunisia. Muscle Nerve 1983; 6: 469–480.CrossRefPubMedGoogle Scholar
  4. 4.
    Ben Hamida M, Marrakchi D. Dystrophie musculaire progressive de type Duchenne en Tunisie. A propos de 13 familles et 31 cas d’une forme en apparence récessive autosomique. J Génét Hum 1980; 28: 1–9.PubMedGoogle Scholar
  5. 5.
    Bonne G, Mercuri E, Muchir A, Urtizberea A, Bécane HM, Recan D, Merlini L, Wehnert M, Boor R, Reuner U, Vorgerd M, Wicklein EM, Eymard B, Duboc D, Penisson-Besnier I, Cuisset JM, Ferrer X, Desguerre I, Lacombe D, Bushby K, Pollitt C, Toniolo D, Fardeau M, Schwartz K, Muntoni F. Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss muscular dystrophy due to mutations of the lamin A/C gene. Ann Neurol 2000; 48: 170–180.CrossRefPubMedGoogle Scholar
  6. 6.
    Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, Ponting CP, Estournet B, Romero NB, Mercuri E, Voit T, Sewry CA, Guicheney P, Muntoni F. Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan. Am J Hum Genet 2001; 69: 1198–1209.CrossRefPubMedGoogle Scholar
  7. 7.
    Bushby KMD. Making sense of the limb-girdle muscular dystrophies. Brain 1999; 122: 1403–1420.CrossRefPubMedGoogle Scholar
  8. 8.
    Bushby KMD, Beckmann JS. The limb-girdle muscular dystrophies – Proposal for a new nomenclature. 30th and 31st ENMC International Workshops, Naarden, The Netherlands, held 6-8 January 1995. Neuromuscul Disord 1995; 5: 337–343.CrossRefPubMedGoogle Scholar
  9. 9.
    Camacho Vanegas O, Bertini E, Zhang RZ, Petrini S, Minosse C, Sabatelli P, Giusti B, Chu ML, Pepe G. Ullrich scleroatonic muscular dystrophy is caused by recessive mutations in collagen type VI. Proc Natl Acad Sci U S A 2001; 98: 7516–7521.CrossRefPubMedGoogle Scholar
  10. 10.
    Campbell KP, Kahl SD. Association of dystrophin and an integral membrane glycoprotein. Nature 1989; 338: 259–262.CrossRefPubMedGoogle Scholar
  11. 11.
    Duchenne de Boulogne GBA. De l’électrisation localisée et son application à la pathologie et à la thérapeutique. 2ª ed. Paris, JB Baillière & Fils, 1861.Google Scholar
  12. 12.
    Duchenne de Boulogne GBA. Recherches sur la paralysie musculaire pseudo-hypertrophique, ou paralysie myo-sclérosique. Arch Gen Med 1868; 11: 5–25, 179–209, 305–321, 421–443, 552–588.Google Scholar
  13. 13.
    Ehmsen J, Poon E, Davies K. The dystrophin-associated protein complex. J Cell Sci 2002; 115: 2801–2803.PubMedGoogle Scholar
  14. 14.
    Emery AEH, Dreifuss FE. Unusual type of benign X-linked muscular dystrophy. J Neurol Neurosurg Psychiat 1966; 29: 338–342.CrossRefPubMedGoogle Scholar
  15. 15.
    Erb W. Muskelbefund bei der juvenilen form der Dystrophia muscularis progressiva. Neurol Zbl 1986; 13: 286–295.Google Scholar
  16. 16.
    Ervasti JM, Campbell KP. Membrane organization of the dystrophin-glycoprotein complex. Cell 1991; 66: 1121–1131.CrossRefPubMedGoogle Scholar
  17. 17.
    Ervasti JM, Ohlendieck K, Kahl SD, et al. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature 1990; 345: 315–319.CrossRefPubMedGoogle Scholar
  18. 18.
    Francke U, Ochs HD, de Martinville B, et al. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa and McLeod syndrome. Am J Hum Genet 1985; 37: 250–267.PubMedGoogle Scholar
  19. 19.
    Frosk P, Del Bigio MR, Wrogemann K, Greenberg CR. Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I. Eur J Hum Genet 2005; 13: 978–982.CrossRefPubMedGoogle Scholar
  20. 20.
    Fulizio L, Nascimbeni AC, Fanin M, Piluso G, Politano L, Nigro V, Angelini C. Molecular and muscle pathology in a series of caveolinopathy patients. Hum Mutat 2005; 25: 82–89.CrossRefPubMedGoogle Scholar
  21. 21.
    Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, Straub V, Robb S, Quinlivan R, Feng L, Jimenez-Mallebrera C, Mercuri E, Manzur AY, Kinali M, Torelli S, Brown SC, Sewry CA, Bushby K, Topaloglu H, North K, Abbs S, Muntoni F. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 2007; 130: 2725–2735.CrossRefPubMedGoogle Scholar
  22. 22.
    Goodfellow PN, Davies KE, Ropers HH. Report of the committee on the genetic constitution of the X and Y chromosomes. Human Gene Mapping 8. Cytogenet Cell Genet 1985; 40: 296–352.Google Scholar
  23. 23.
    Gowers WR. A lecture on myopathy and a distal form. Br Med J 1902; 2: 89.CrossRefPubMedGoogle Scholar
  24. 24.
    Guglieri M, Magri F, D'Angelo MG, Prelle A, Morandi L, Rodolico C, Cagliani R, Mora M, Fortunato F, Bordoni A, Del Bo R, Ghezzi S, Pagliarani S, Lucchiari S, Salani S, Zecca C, Lamperti C, Ronchi D, Aguennouz M, Ciscato P, Di Blasi C, Ruggieri A, Moroni I, Turconi A, Toscano A, Moggio M, Bresolin N, Comi GP. Clinical, molecular, and protein correlations in a large sample of genetically diagnosed Italian limb girdle muscular dystrophy patients. Hum Mutat 2008; 29: 258–266.CrossRefPubMedGoogle Scholar
  25. 25.
    Guglieri M, Straub V, Bushby K, Lochmüller H. Limb-girdle muscular dystrophies. Curr Opin Neurol 2008; 21: 576–584.CrossRefPubMedGoogle Scholar
  26. 26.
    Hicks D, Lampe AK, Barresi R, Charlton R, Fiorillo C, Bonnemann CG, Hudson J, Sutton R, Lochmüller H, Straub V, Bushby K. A refined diagnostic algorithm for Bethlem myopathy. Neurology 2008; 70: 1192–1199.CrossRefPubMedGoogle Scholar
  27. 27.
    Hillaire D, Leclerc A, Fauré S, Topaloglu H, Chiannilkulchaï N, Guicheney P, Grinas L, Legos P, Philpot J, Evangelista T, et al. Localization of merosin-negative congenital muscular dystrophy to chromosome 6q2 by homozygosity mapping. Hum Mol Genet 1994; 3: 1657–1661.CrossRefPubMedGoogle Scholar
  28. 28.
    Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987; 51: 919–928.CrossRefPubMedGoogle Scholar
  29. 29.
    Jöbsis GJ, Keizers H, Vreijling JP, de Visser M, Speer MC, Wolterman RA, Baas F, Bolhuis PA. Type VI collagen mutations in Bethlem myopathy, an autosomal dominant myopathy with contractures. Nat Genet 1996; 14: 113–115.CrossRefPubMedGoogle Scholar
  30. 30.
    Koenig M, Hoffman EP, Bertelson CJ, et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 1987; 50: 509–517.CrossRefPubMedGoogle Scholar
  31. 31.
    Kunkel LM and co-authors. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 1986; 322: 73–77.CrossRefPubMedGoogle Scholar
  32. 32.
    Kunkel LM, Monaco AP, Middlesworth W, et al. Specific cloning of DNA fragments absent from the DNA of a male patient with a X-chromosome deletion. Proc Natl Acad Sci USA 1985; 82: 4778–4782.CrossRefPubMedGoogle Scholar
  33. 33.
    Landouzy L, Dejerine J. De la myopathie atrophique progressive (myopathie héréditaire, débutant dans l’enfance par la face, sans altération du système nerveux). CR Acad Sci 1884; 98: 53–55.Google Scholar
  34. 34.
    Laval SH, Bushby KMD. Limb-girdle muscular dystrophies – from genetics to molecular pathology. Neuropathol Appl Neurobiol 2004; 30: 91–105.CrossRefPubMedGoogle Scholar
  35. 35.
    Liu J, Aoki M, Illa I, Wu C, Fardeau M, Angelini C, Serrano C, Urtizberea JA, Hentati F, Hamida MB, Bohlega S, Culper EJ, Amato AA, Bossie K, Oeltjen J, Bejaoui K, McKenna-Yasek D, Hosler BA, Schurr E, Arahata K, de Jong PJ, Brown RH Jr. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 1998; 20: 31–36.CrossRefPubMedGoogle Scholar
  36. 36.
    Mercuri E, Yuva Y, Brown SC, Brockington M, Kinali M, Jungbluth H, Feng L, Sewry CA, Muntoni F. Collagen VI involvement in Ullrich syndrome: a clinical, genetic, and immunohistochemical study. Neurology 2002; 58: 1354–1359.PubMedGoogle Scholar
  37. 37.
    Merlini L, Kaplan J-C, Navarro C, Barois A, Bonneau D, Brasa J, Echenne B, Gallano P, Jarre L, Jeanpierre M, Kalaydjieva L, Leturcq F, Levi-Gomes A, Toutain A, Tournev I, Urtizberea A, Vallat J-M, Voit T, Warter J-M. Homogeneous phenotype of the gypsy limb-girdle MD with the gamma-sarcoglycan C283Y mutation. Neurology 2000; 54: 1075–1079.PubMedGoogle Scholar
  38. 38.
    Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, Masetti E, Mazzocco M, Egeo A, Donati MA, Volonte D, Galbiati F, Cordone G, Bricarelli FD, Lisanti MP, Zara F. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nat Genet 1998; 18: 365–368.CrossRefPubMedGoogle Scholar
  39. 39.
    Muntoni F, Valero de Bernabe B, Bittner R, Blake D, van Bokhoven H, Brockington M, Brown S, Bushby K, Campbell KP, Fiszman M, Gruenewald S, Merlini L, Quijano-Roy S, Romero N, Sabatelli P, Sewry CA, Straub V, Talim B, Topaloglu H, Voit T, Yurchenco PD, Urtizberea JA, Wewer UM, Guicheney P. 114th ENMC International Workshop on Congenital Muscular Dystrophy (CMD) 17-19 January 2003, Naarden, The Netherlands: (8th Workshop of the International Consortium on CMD; 3rd Workshop of the MYO-CLUSTER project GENRE). Neuromuscul Disord 2003; 13: 579–588.CrossRefPubMedGoogle Scholar
  40. 40.
    Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, Hayashi YK, Tsukahara T, Arahata K. Emerin deficiency at the nuclear membrane in patients with Emery–Dreifuss muscular dystrophy. Nat Genet 1996; 12: 254–259.CrossRefPubMedGoogle Scholar
  41. 41.
    Piccolo F, Jeanpierre M, Leturcq F, Dodé C, Azibi K, Toutain A, Merlini L, Jarre L, Navarro C, Krishnamoorthy R, Tomé FM, Urtizberea JA, Beckmann JS, Campbell KP, Kaplan JC. A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India. Hum Mol Genet 1996; 5: 2019–2022.CrossRefPubMedGoogle Scholar
  42. 42.
    Rivas E, Teijeira S, Dos Santos MR, Porrit I, Lecturcq F, Fernández JM, Navarro C. Beta-sarcoglycanophaty (LGMD2E) in a Spanish family. Acta Myologica*** 2004; XXIII: 159–162.Google Scholar
  43. 43.
    Sáenz A, Leturcq F, Cobo AM, Poza JJ, Ferrer X, Otaegui D, Camaño P, Urtasun M, Vílchez J, Gutiérrez-Rivas E, Emparanza J, Merlini L, Paisán C, Goicoechea M, Blázquez L, Eymard B, Lochmuller H, Walter M, Bonnemann C, Figarella-Branger D, Kaplan JC, Urtizberea JA, Martí-Massó JF, López de Munain A. LGMD2A: genotype-phenotype correlations based on a large mutational survey on the calpain 3 gene. Brain 2005; 128: 732–742.CrossRefPubMedGoogle Scholar
  44. 44.
    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.CrossRefPubMedGoogle Scholar
  45. 45.
    Taylor, E. W. Progressive vagus-glossopharyngeal paralysis with ptosis: contribution to group of family diseases. J Nerv Ment Dis 1915; 42: 129–139.CrossRefGoogle Scholar
  46. 46.
    Teijeira S, Teijeiro A, Fernández R, Navarro C. Subsarcolemmal expression of utrophin in neuromuscular disorders: an immunohistochemical study of 80 cases. Acta Neuropathol 1998; 96: 481–486.CrossRefPubMedGoogle Scholar
  47. 47.
    Walton JN, Nattrass FJ. On the classification, natural history and treatment of the myopathies. Brain 1954; 77: 169–231.CrossRefPubMedGoogle Scholar
  48. 48.
    Yoshida M, Ozawa E. Glycoprotein complex anchoring dystrophin to sarcolemma. J Biochem 1990; 108: 748–752.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Carmen Navarro
    • 1
    Email author
  • Susana Teijeira
    • 1
  • Beatriz San Millán
    • 1
  1. 1.Department of Pathology and NeuropathologyUniversity Hospital of Vigo (Meixoeiro)PontevedraSpain

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