Abstract
Limb girdle muscular dystrophy type 2 G (LGMD2G) is caused by mutations in the telethonin gene. Only few families were described presenting this disease, and they are mainly Brazilians. Here, we identified one additional case carrying the same common c.157C > T mutation in the telethonin gene but with an atypical histopathological muscle pattern. In a female patient with a long duration of symptoms (46 years), muscle biopsy showed, in addition to telethonin deficiency, the presence of nemaline rods, type 1 fiber predominance, nuclear internalization, lobulated fibers, and mitochondrial paracrystalline inclusions. Her first clinical signs were identified at 8 years old, which include tiptoe walking, left lower limb deformity, and frequent falls. Ambulation loss occurred at 41 years old, and now, at 54 years old, she presented pelvic girdle atrophy, winging scapula, foot deformity with incapacity to perform ankle dorsiflexion, and absent tendon reflexes. The presence of nemaline bodies could be a secondary phenomenon, possibly associated with focal Z-line abnormalities of a long-standing disease. However, these new histopathological findings, characteristic of congenital myopathies, expand muscle phenotypic variability of telethoninopathy.
Abbreviations
- LGMD:
-
Limb girdle muscular dystrophy
References
Almeida CF, Lima BL, Onofre-Oliveira PCG, Pavanello RCM, Zatz M, Vainzof M (2012) G.P.40 LGMD2G with clinical presentation of congenital muscular dystrophy: A rare phenotype. Neuromuscul Disord 22:831
Banker BQ and Engel AG (2004) Basic reactions of muscle. In: Engel AG and Franzini-Armstrong C (eds) Myology, vol. 1, Chapter 30 3rd edn. McGraw-Hill, New York, p 703
Chae J, Minami N, Jin Y et al (2001) Calpain 3 gene mutations: genetic and clinico-pathologic findings in limb-girdle muscular dystrophy. Neuromuscul Disord 11:547–555
Engel AG, Banker BQ (2004) Ultrastructural changes in diseased muscle. In: Engel AG, Franzini-Armstrong C (eds) Myology, vol 1, 3rd edn. McGraw-Hill, New York, p 786
Ferreiro A, Mezmezian M, Olivé M et al (2011) Telethonin-deficiency initially presenting as a congenital muscular dystrophy. Neuromuscul Disord 21:433–438
Gamez J, Navarro C, Andreu AL et al (2001) Autosomal dominant limb-girdle muscular dystrophy: a large kindred with evidence for anticipation. Neurology 56:450–454
Gregorio CC, Trombitás K, Centner T et al (1998) The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity. J Cell Biol 143:1013–1027
Irodenko VS, Lee HS, de Armond SJ, Layzer RB (2009) Adult nemaline myopathy with trabecular muscle fibers. Muscle Nerve 39:871–875
Lima BL, Gouveia TL, Pavanello RC, Faulkner G, Valle G, Zatz M, Vainzof M (2005) L.P.3.02. LGMD2G: screening for mutations in a large sample of Brazilian patients allows the identifications of new cases [abstract] to Neuromuscul Disord 15:702
Moreira ES, Vainzof M, Marie SK, Sertié AL, Zatz M, Passos-Bueno MR (1997) The seventh form of autosomal recessive limb-girdle muscular dystrophy is mapped to 17q11-12. Am J Hum Genet 61:151–159
Moreira ES, Wiltshire TJ, Faulkner G et al (2000) Limb-girdle muscular dystrophy type 2 G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat Genet 24:163–166
Negrão L, Matos A, Geraldo A, Rebelo O (2010) Limb-girdle muscular dystrophy in a Portuguese patient caused by a mutation in the telethonin gene. Acta Myol 29:21–24
Olivé M, Shatunov A, Gonzalez L et al (2008) Transcription-terminating mutation in telethonin causing autosomal recessive muscular dystrophy type 2 G in a European patient. Neuromuscul Disord 18:929–933
Passos-Bueno MR, Vainzof M, Moreira ES, Zatz M (1999) Seven autosomal recessive limb-girdle muscular dystrophies in the Brazilian population: from LGMD2A to LGMD2G. Am J Med Genet 82:392–398
Vainzof M, Bushby K (2010) Muscular dystrophies presenting with proximal muscle weakness. In: Karpati G, Hilton-Jones D, Bushby K, Griggs RC (eds) Disorders of voluntary muscle, 8th edn. Cambridge University Press, Cambridge, pp 230–256
Vainzof M, Moreira ES, Suzuki OT et al (2002) Telethonin protein expression in neuromuscular disorders. Biochim Biophys Acta 1588:33–40
Valle G, Faulkner G, De Antoni A et al (1997) Telethonin, a novel sarcomeric protein of heart and skeletal muscle. FEBS Lett 415:163–168
Waddell LB, Lek M, Bahlo M et al (2012) The identification of LGMD2G (TCAP) in Australia. Neuromuscul Disord 22:831–832
Wallgren-Pettersson C, Sewry CA, Nowak KJ, Laing NG (2011) Nemaline myopathies. Semin Pediatr Neurol 18:230–238
Wengert O, Meisel A, Kress W et al (2011) Progressive external ophthalmoplegia as initial manifestation of sporadic late-onset nemaline myopathy. J Neurol 258:915–917
Yee WPZ, Kathiravelu P, Lai P (2007) Limb girdle muscular dystrophy 2 G and a novel TCAP mutation in ethnic Chinese. Neuromuscul Disord 17:814
Zhang S, Londhe P, Zhang M, Davie JK (2011) Transcriptional analysis of the titin cap gene. Mol Genet Genomics 285:261–272
Acknowlegments
We thank Cleides Campos de Oliveira, Simone Ferreira do Nascimento, Marta Canovas, and Leticia Nogueira for the technical assistance. We also thank FAPESP, CNPq-INCT, FINEP, and CAPES-COFECUB for the financial support.
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Paim, J.F., Cotta, A., Vargas, A.P. et al. Muscle Phenotypic Variability in Limb Girdle Muscular Dystrophy 2 G. J Mol Neurosci 50, 339–344 (2013). https://doi.org/10.1007/s12031-013-9987-6
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DOI: https://doi.org/10.1007/s12031-013-9987-6