Abstract
Limb-girdle muscular dystrophy 9LGMD) type 2A (LGMD2A; MIM253600) is an autosomal recessive disorder belonging to the group of progressive MDs. LGMD2A is characterized by symmetrical atrophy of the pelvic, scapular, and trunk muscles, elevated serum creatine kinase and a necrotic-regeneration pattern on muscular biopsies (1– 2). The study of these biopsies show that the integrity of the dystrophin-associated complex is preserved in these patients, because immunohistochemical staining for dystrophin, merosin, or the various sarcoglycan (SG) proteins is normal (2). Other than that, there are no specific diagnostic criteria, which explains why, despite having been properly described over a century ago (3), this field has generated much heated controversy, but this clinical entity remained difficult to recognize.
Keywords
- Polymerase Chain Reaction Product
- Polymerase Chain Reaction Amplification
- Muscle Biopsy
- Nest Polymerase Chain Reaction
- Heteroduplex Analysis
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Fardeau, M., Hillaire, D., Mignard, C., Feingold, N., Mignard, D., de Ubeda, B., et al. (1996) Juvenile limb-girdle muscular dystrophy: clinical, histopathological, and genetic data from a small community living in the Reunion Island. Brain 119, 295–308.
Beckmann, J. S. and Fardeau, M. (1998) Limb-girdle muscular dystrophies, in Neuromuscular disorders: Clinical and Molecular Genetics (Emery, A. E. H., ed.), Chichester, UK,. 123–156.
Erb, W. (1884) Ueber die “juvenile form” der progressiven muskelatrophie ihre Beziehungen zur sogenannten pseudohypertrophie der muskeln. Deutsches Archiv fur Klinische Medizin. 34, 467–519.
Campbell, K. P. (1995) Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell 80, 675–679.
Roberds, S. L., Leturcq, F., Allamand, V., Piccolo, F., Jeanpierre, M., Anderson, R. D., et al. (1994) Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy. Cell 78, 625–633.
Noguchi, S., McNally, E. M., Ben Othmane, K., Hagiwara, Y., Mizuno, Y., Yoshida, M., et al. (1995) Mutations in the dystrophin-associated protein-sarcoglycan in chromosome 13 muscular dystrophy. Science 270, 819–822.
Lim, L. E., Duclos, F., Broux, O., Bourg, N., Sunada Y., Allamand, V., et al. (1995)-Sarcoglycan (43 DAG): characterization and role in limb-girdle muscular dystrophy linked to chromosome 4q12. Nature Genet. 11, 257–265.
Bönnemann, C. G., Modi, R., Noguchi, S., Mizuno, Y., Yoshida, M., Gussoni, E., et al. (1995)-Sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Nature Genet. 11, 266–273.
Nigro, V., deSà Moreira, E., Piluso, G., Vainzof, M., Belsito, A., Politano, L., et al. (1996) Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the-sarcoglycan gene. Nature Genet. 14, 195–198.
Bashir, R., Strachan, T., Keers, S., Stephenson, A., Mahjneh, I., Marconi, G., Nashef, L., and Bushby, K. M. D. (1994) A gene for autosomal recessive limbgirdle muscular dystrophy maps to chromosome 2p. Hum. Mol. Genet. 3, 455–457.
Bashir, R., Britton, S., Strachan, T., Keers, S., Vafiadaki, E., Lako, M., et al. (1998) A gene related to the C. elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B. Nat. Genet. 20, 37–42.
Liu, J., Aoki, M., Illa, I., Wu, C., Fardeau, M., Angelini, C., Serrano, C., et al. (1998) Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and linb-girdle muscular dystrophy. Nat. Genet. 24, 31–36.
Moreira, E. S., Wiltshire, T. J., Faulkner, G., Nilforoushan, A., Vainzof, M., et al. (2000) Limb-girdle muscular dystrophy type 2G is caused by mutations in the gene encoding the sarcomeric protein telethonin. Nat. Genet. 24, 163–166.
Moreira, E. S., Vainzof, M., Marie, S. K., SertiA. L., Zatz, M., and Passos-Bueno, M.-R. (1997) The seventh form of autosomal recessive Limb-girdle muscular dystrophy is mapped to 17q11-12. Am. J. Hum. Genet. 61, 151–156.
Beckmann, J. S., Richard, I., Hillaire, D., Broux, O., Antignac, C., Bois, E., Cann, H., et al. (1991) A gene for limb-girdle muscular dystrophy maps to chromosome 15 by linkage analysis. C. R. Acad. Sci. Paris III 312, 141–148.
Fougerousse, F., Broux, O., Richard, I., Allamand, V., Pereira de Souza, A., Bourg, N., et al. (1994) Mapping of a chromosome 15 region involved in limbgirdle muscular dystrophy. Hum. Mol. Genet. 3, 285–293.
Allamand, V., Broux, O., Richard, I., Fougerousse, F., Chiannilkulchai, N., Bourg, N., et al. (1995) Preferential localization of the limb-girdle muscular dystrophy type 2A gene in the proximal part of a 1 cM 15q15.1-q15.3 interval. Am. J. Hum. Genet. 56, 1417–1430.
Chiannilkulchai, N., Pasturaud, P., Richard, I., Auffray, C., and Beckmann, J. S. (1995) A primary expression map of chromosome 15q15 region containing the recessive form of limb-girdle muscular dystrophy (LGMD2A) gene. Hum. Mol. Genet. 4, 717–726.
Richard, I., Broux, O., Allamand, V., Fougerousse, F., Chiannilkulchai, N., Bourg, N., et al. (1995) Mutations in the proteolytic enzyme, calpain 3, cause limb-girdle muscular dystrophy type 2A. Cell 81, 27–40.
Sorimachi, H., Imajoh-Ohmi, S., Emori, Y., Kawasaki, H., Ohno, S., Minami, Y., and Suzuki, K. (1989) Molecular cloning of a novel mammalian calcium-dependent protease distinct from both m-and mu-type. Specific expression of the mRNA in skeletal muscle. J. Biol. Chem. 264, 20,106–20,111.
Croall, D. E. and Demartino, G. N. (1991) Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol. Rev. 71, 813–847.
Suzuki, K., Sorimachi, H., Yoshizawa, T., Kinbara, K., and Ishiura, S. 1995. Calpain: novel family members, activation, and physiological function. Biol. Chem. 376, 523–529.
Sorimachi, H., Ishiura, S., and Suzuki, K. (1997) Structure and physiological function of calpains. Biochem. J. 328, 721–732.
Richard, I. and Beckmann, J. S. (1995) How neutral are synonymous codon mutations Nature Genet. 10, 259.
Richard, I., Brenguier, L., Din, P., Roudaut, C., Bady, B., Burgunder, J.-M., et al. (1997) Multiple Independant molecular etiology for LGMD2A patients from various geographical origins. Am. J. Hum. Genet. 60, 1128–1138.
Din, P., Leturcq, F., Richard, I., Piccolo, F., Yalnizoglu, D., de Toma, C., Broux, O., et al. (1997) A biochemical, genetic and clinical survey of autosomal recessive limb-girdle muscular dystrophies in Turkey. Ann. Neurol. 42, 222–229.
Richard, I., Roudaut, C., Saenz, A., Pogue, R., et al. (1999) Calpainopathy: A survey of mutations and polymorphisms. Am. J. Hum. Genet. 64, 1524–1540.
Fougerousse, F., Durand, M., Suel, L., Pourquié O., Delezoide, A-L., Roméro, N., Abitbol, M., and Beckmann, J. S. (1998) Expression of genes (CAPN3, SGCA, SGCB, and TTN) involved in progressive muscular dystrophies during early human development. Genomics 48, 145–156.
Ma, H., Fukiage, C., Azuma, M., and Shearer, T. R. (1998) Cloning and expression of mRNA for calpain Lp82 from rat lens: splice variant of p94. Invest. Ophthalmol. Visual Sci. 39, 454–461.
Herasse, M., Ono, Y., Fougerousse, F., Kimura E., Beley, C., Montarras, D., Pinset, C., et al. (1999) Expression and functional characteristics of Calpain 3 isoforms generated through tissue-specific transcriptional and post-transcriptional events. Mol. Cell. Biol. 19, 4047–4055.
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K., and Sekiya, T. (1989) Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. Natl. Acad. Sci. USA 86, 2766–2770.
Keen, J., Lester, D., Inglehearn, C., Curtis, A., and Bhattacharya, S. (1991) Rapid detection of single base mismatches as heteroduplexes on Hydrolink gels. Trends Genet. 7, 5.
Chelly, J., Condorcet, J.-P., Kaplan, J. C., and Kahn, A. (1989) Illegitimate transcription: Transcription of any genes in any cell type. Proc. Natl. Acad. Sci. USA 86, 2617–2621.
Don, R. H., Cox, P. T., Wainwright, B. J., Baker, K., and Mattick, J. S. (1991) ’Touchdown’ PCR to circumvent spurious priming during gene amplification. Nucleic Acid Res. 19, 4008.
Myers, R. M., Maniatis, T., and Lerman, L. S. (1987) Detection and localisation of single base changes by denaturing gradient gel electrophoresis. Methods Enzymol. 155, 501–527.
Verpi, E., Biasotto, M., Meo, T., and Tosi, M. (1994). Efficient detection of point mutations on color-coded strands of target DNA. Proc. Natl. Acad. Sci. USA 91, 1873–1877.
Roberts, R. G., Bentley, D. R., and Bobrow, M. (1993) Infidelity in the structure of ectopic transcripts: a novel exon in lymphocyte dystrophin transcripts. Human Mut. 2, 293–299.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Richard, I., Beckmann, J. (2001). Molecular Diagnosis of Calpainopathies. In: Bushby, K.M., Anderson, L.V. (eds) Muscular Dystrophy. Methods in Molecular Medicine, vol 43. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-138-8:273
Download citation
DOI: https://doi.org/10.1385/1-59259-138-8:273
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-695-6
Online ISBN: 978-1-59259-138-1
eBook Packages: Springer Protocols