Histopathological and Genetic Features of Patients with Limb Girdle Muscular Dystrophy Type 2C

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Abstract

Objective: In this study, it was aimed to describe the clinical, histopathological and genetic features of 20 patients with gamma sarcoglycanopathy confirmed by muscle biopsies and genetic analysis.

Material and Method: We retrospectively reviewed 20 patients from whom muscle biopsy specimens were obtained between 2007 and 2012. All patients were clinically diagnosed as muscular dystrophy and biopsy materials were collected from five different centers of neurological disorders. All DNAs were extracted from muscle tissues or blood samples of patients and genetic tests (mutation analyses for gamma sarcoglycan gene and deletion-duplication analyses for all 4 sarcoglycan genes) were performed.

Results: The mean age of the patients was 7.6 years (2 -21 years). Only one case (5%) was older than 14 years. The mean CPK level was 10311 U/L (1311 - 35000 U∕L). There were 4 siblings in these series. Expression defects of gamma sarcoglycan staining were determined in (15 males, and 5 females) all patients with muscle biopsy specimens. But only in 9 of them, disease-causing defects could be determined with genetic analyses.

Conclusion: The present study has demonstrated that both examination of muscle biopsy specimens and DNA analysis remain important methods in the differential diagnosis of muscular dystrophies. Because dystrophinopathies and sarcoglycanopathies have similar clinical manifestation.

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  • 1. Dubowitz V Sewry CA Oldfors A. Muscle Biopsy: A practical approach. Philadelphia: Saunders; 2013.276-302.

  • 2. Sandonà D Betto R. Sarcoglycanopathies: Molecular pathogenesis and therapeutic prospects. Expert Rev Mol Med. 2009;11:e28.

  • 3. Ben Jelloun-Dellagi S Chaffey P Hentati F Ben Hamida C Tome F Colin H Dellagi K Kaplan JC Fardeau M Ben Hamida M. Presence of normal dystrophin in Tunisian severe childhood autosomal recessive muscular dystrophy. Neurology. 1990;40:1903.

  • 4. Pogue R Anderson LV Pyle A Sewry C Pollitt C Johnson MA Davison K Moss JA Mercuri E Muntoni F Bushby KM. Strategy for mutation analysis in the autosomal recessive limb-girdle muscular dystrophies. Neuromuscul Disord. 2001;11:80-7.

  • 5. Moreira ES Vainzof M Suzuki OT Pavanello RC Zatz M Passos-Bueno MR. Genotype-phenotype correlations in 35 Brazilian families with sarcoglycanopathies including the description of three novel mutations. J Med Genet. 2003;40:E12.

  • 6. Gulati S Leekha S Sharma MC Kalra V. Gamma-sarcoglycanopathy. Indian Pediatr. 2003;40:1077-81.

  • 7. Azibi K Bachner L Beckmann J S Matsumura K Hamouda E Chaouch M Chaouch A Ait-Ouarab R Vignal A Weissenbach J. Severe childhood autosomal recessive muscular dystrophy with the deficiency of the 50 kDa dystrophin-associated glycoprotein maps to chromosome 13q12. Hum Molec Genet. 1993;2:1423-28.

  • 8. El Kerch F Sefiani A Azibi K Boutaleb N Yahyaoui M Bentahila A Vinet MC Leturcq F Bachner L Beckmann J et al. Linkage analysis of families with severe childhood autosomal recessive muscular dystrophy in Morocco indicates genetic homogeneity of the disease in North Africa. J Med Genet. 1994;31: 342-3.

  • 9. Lasa A Piccolo F de Diego C Jeanpierre M Colomer J Rodríguez MJ Urtizberea JA Baiget M Kaplan J Gallano P. Severe limb girdle muscular dystrophy in Spanish gypsies: Further evidence for a founder mutation in the gamma-sarcoglycan gene. Eur J Hum Genet. 1998;6:396-9.

  • 10. Klinge L Dekomien G Aboumousa A Charlton R Epplen JT Barresi R Bushby K Straub V. Sarcoglycanopathies: Can muscle immunoanalysis predict the genotype? Neuromuscul Disord. 2008;18:934-41.

  • 11. Trabelsi M Kavian N Daoud F Commere V Deburgrave N Beugnet C Llense S Barbot JC Vasson A Kaplan JC Leturcq F Chelly J. Revised spectrum of mutations in sarcoglycanopathies. Eur J Hum Genet. 2008;16:793-803.

  • 12. Ferreira AF Carvalho MS Resende MB Wakamatsu A Reed UC Marie SK. Phenotypic and immunohistochemical characterization of sarcoglycanopathies. Clinics (Sao Paulo). 2011;66:1713-19.

  • 13. Jung D Leturcq F Sunada Y Duclos F Tome FMS Moomaw C Merlini L Azibi K Chaouch M Slaughter C Fardeau M Kaplan JC Campbell KP. Absence of gamma-sarcoglycan (35 DAG) in autosomal recessive muscular dystrophy linked to chromosome 13q12. FEBS Lett. 1996:381: 15-20.

  • 14. Kefi M Amouri R Driss A Ben Hamida C Ben Hamida M Kunkel LM Hentati F. Phenotype and sarcoglycan expression in Tunisian LGMD 2C patients sharing the same del521-T mutation. Neuromuscul Disord. 2003;13:779-87.

  • 15. Navarro C Teijeira S. Neuromuscular disorders in the Gypsy ethnic group: A short review. Acta Myol. 2003; 22: 11-14.

  • 16. McNally EM Duggan D Gorospe J R Bonnemann C G Fanin M Pegoraro E Lidov HG Noguchi S Ozawa E Finkel RS Cruse RP Angelini C Kunkel LM Hoffman EP. Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy. Hum Molec Genet. 1996;5:1841-7.

  • 17. Merlini L Kaplan JC 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 JM Voit T Warter JM. Homogeneous phenotype of the gypsy limb-girdle MD with the gamma-sarcoglycan C283Y mutation. Neurology. 2000;54:1075-9.

  • 18. Dinçer P Akçören Z Demir E Richard I Sancak O Kale G Ozme S Karaduman A Tan E Urtizberea JA Beckmann JS Topaloğlu H. A cross section of autosomal recessive limb-girdle muscular dystrophies in 38 families. J Med Genet. 2000;37:361-7.

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