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. 1998 Nov;35(11):951–953. doi: 10.1136/jmg.35.11.951

A first missense mutation in the delta sarcoglycan gene associated with a severe phenotype and frequency of limb-girdle muscular dystrophy type 2F (LGMD2F) in Brazilian sarcoglycanopathies.

E S Moreira 1, M Vainzof 1, S K Marie 1, V Nigro 1, M Zatz 1, M R Passos-Bueno 1
PMCID: PMC1051491  PMID: 9832045

Abstract

Among the heterogeneous group of autosomal recessive limb-girdle muscular dystrophies (AR LGMDs), the sarcoglycanopathies (LGMD2C-2F) represent a subgroup characterised by defects in the gamma, alpha, beta, and delta sarcoglycan genes, respectively. Genotype-phenotype correlations in these forms of AR LGMD are important to enhance our understanding of protein function. Regarding LGMD2F, only two homozygous frameshift mutations have been reported to date in patients with a severe phenotype. In the present report, through screening 23 unrelated AR LGMD patients, we identified three subjects with LGMD2F, two with a previously reported frameshift mutation and the other homozygous for a new missense mutation in the delta sarcoglycan gene. Interestingly, this new mutation is also associated with a severe clinical course. In addition, our results suggest that this form of severe AR LGMD is not very rare in our population.

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Selected References

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  1. Ben Othmane K., Speer M. C., Stauffer J., Blel S., Middleton L., Ben Hamida C., Etribi A., Loeb D., Hentati F., Roses A. D. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy (LGMD2C) Am J Hum Genet. 1995 Sep;57(3):732–734. [PMC free article] [PubMed] [Google Scholar]
  2. Bushby K. M., Beckmann J. S. The limb-girdle muscular dystrophies--proposal for a new nomenclature. Neuromuscul Disord. 1995 Jul;5(4):337–343. doi: 10.1016/0960-8966(95)00005-8. [DOI] [PubMed] [Google Scholar]
  3. Bönnemann C. G., Modi R., Noguchi S., Mizuno Y., Yoshida M., Gussoni E., McNally E. M., Duggan D. J., Angelini C., Hoffman E. P. Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex. Nat Genet. 1995 Nov;11(3):266–273. doi: 10.1038/ng1195-266. [DOI] [PubMed] [Google Scholar]
  4. Bönnemann C. G., Passos-Bueno M. R., McNally E. M., Vainzof M., de Sá Moreira E., Marie S. K., Pavanello R. C., Noguchi S., Ozawa E., Zatz M. Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E). Hum Mol Genet. 1996 Dec;5(12):1953–1961. doi: 10.1093/hmg/5.12.1953. [DOI] [PubMed] [Google Scholar]
  5. Campbell K. P. Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage. Cell. 1995 Mar 10;80(5):675–679. doi: 10.1016/0092-8674(95)90344-5. [DOI] [PubMed] [Google Scholar]
  6. Carrié A., Piccolo F., Leturcq F., de Toma C., Azibi K., Beldjord C., Vallat J. M., Merlini L., Voit T., Sewry C. Mutational diversity and hot spots in the alpha-sarcoglycan gene in autosomal recessive muscular dystrophy (LGMD2D). J Med Genet. 1997 Jun;34(6):470–475. doi: 10.1136/jmg.34.6.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duggan D. J., Manchester D., Stears K. P., Mathews D. J., Hart C., Hoffman E. P. Mutations in the delta-sarcoglycan gene are a rare cause of autosomal recessive limb-girdle muscular dystrophy (LGMD2). Neurogenetics. 1997 May;1(1):49–58. doi: 10.1007/s100480050008. [DOI] [PubMed] [Google Scholar]
  8. Lim L. E., Duclos F., Broux O., Bourg N., Sunada Y., Allamand V., Meyer J., Richard I., Moomaw C., Slaughter C. Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12. Nat Genet. 1995 Nov;11(3):257–265. doi: 10.1038/ng1195-257. [DOI] [PubMed] [Google Scholar]
  9. McNally E. M., Duggan D., Gorospe J. R., Bönnemann C. G., Fanin M., Pegoraro E., Lidov H. G., Noguchi S., Ozawa E., Finkel R. S. Mutations that disrupt the carboxyl-terminus of gamma-sarcoglycan cause muscular dystrophy. Hum Mol Genet. 1996 Nov;5(11):1841–1847. doi: 10.1093/hmg/5.11.1841. [DOI] [PubMed] [Google Scholar]
  10. McNally E. M., Passos-Bueno M. R., Bönnemann C. G., Vainzof M., de Sá Moreira E., Lidov H. G., Othmane K. B., Denton P. H., Vance J. M., Zatz M. Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation. Am J Hum Genet. 1996 Nov;59(5):1040–1047. [PMC free article] [PubMed] [Google Scholar]
  11. McNally E. M., Yoshida M., Mizuno Y., Ozawa E., Kunkel L. M. Human adhalin is alternatively spliced and the gene is located on chromosome 17q21. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9690–9694. doi: 10.1073/pnas.91.21.9690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Monckton D. G., Wong L. J., Ashizawa T., Caskey C. T. Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses. Hum Mol Genet. 1995 Jan;4(1):1–8. doi: 10.1093/hmg/4.1.1. [DOI] [PubMed] [Google Scholar]
  13. Nigro V., Piluso G., Belsito A., Politano L., Puca A. A., Papparella S., Rossi E., Viglietto G., Esposito M. G., Abbondanza C. Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein. Hum Mol Genet. 1996 Aug;5(8):1179–1186. doi: 10.1093/hmg/5.8.1179. [DOI] [PubMed] [Google Scholar]
  14. Nigro V., de Sá Moreira E., Piluso G., Vainzof M., Belsito A., Politano L., Puca A. A., Passos-Bueno M. R., Zatz M. Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene. Nat Genet. 1996 Oct;14(2):195–198. doi: 10.1038/ng1096-195. [DOI] [PubMed] [Google Scholar]
  15. Noguchi S., McNally E. M., Ben Othmane K., Hagiwara Y., Mizuno Y., Yoshida M., Yamamoto H., Bönnemann C. G., Gussoni E., Denton P. H. Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy. Science. 1995 Nov 3;270(5237):819–822. doi: 10.1126/science.270.5237.819. [DOI] [PubMed] [Google Scholar]
  16. Ozawa E., Yoshida M., Suzuki A., Mizuno Y., Hagiwara Y., Noguchi S. Dystrophin-associated proteins in muscular dystrophy. Hum Mol Genet. 1995;4(Spec No):1711–1716. doi: 10.1093/hmg/4.suppl_1.1711. [DOI] [PubMed] [Google Scholar]
  17. Passos-Bueno M. R., Moreira E. S., Vainzof M., Marie S. K., Zatz M. Linkage analysis in autosomal recessive limb-girdle muscular dystrophy (AR LGMD) maps a sixth form to 5q33-34 (LGMD2F) and indicates that there is at least one more subtype of AR LGMD. Hum Mol Genet. 1996 Jun;5(6):815–820. doi: 10.1093/hmg/5.6.815. [DOI] [PubMed] [Google Scholar]
  18. Piccolo F., Jeanpierre M., Leturcq F., Dodé C., Azibi K., Toutain A., Merlini L., Jarre L., Navarro C., Krishnamoorthy R. A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India. Hum Mol Genet. 1996 Dec;5(12):2019–2022. doi: 10.1093/hmg/5.12.2019. [DOI] [PubMed] [Google Scholar]
  19. Piccolo F., Roberds S. L., Jeanpierre M., Leturcq F., Azibi K., Beldjord C., Carrié A., Récan D., Chaouch M., Reghis A. Primary adhalinopathy: a common cause of autosomal recessive muscular dystrophy of variable severity. Nat Genet. 1995 Jun;10(2):243–245. doi: 10.1038/ng0695-243. [DOI] [PubMed] [Google Scholar]
  20. Roberds S. L., Anderson R. D., Ibraghimov-Beskrovnaya O., Campbell K. P. Primary structure and muscle-specific expression of the 50-kDa dystrophin-associated glycoprotein (adhalin). J Biol Chem. 1993 Nov 15;268(32):23739–23742. [PubMed] [Google Scholar]
  21. Roberds S. L., Leturcq F., Allamand V., Piccolo F., Jeanpierre M., Anderson R. D., Lim L. E., Lee J. C., Tomé F. M., Romero N. B. Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy. Cell. 1994 Aug 26;78(4):625–633. doi: 10.1016/0092-8674(94)90527-4. [DOI] [PubMed] [Google Scholar]
  22. Vainzof M., Passos-Bueno M. R., Canovas M., Moreira E. S., Pavanello R. C., Marie S. K., Anderson L. V., Bonnemann C. G., McNally E. M., Nigro V. The sarcoglycan complex in the six autosomal recessive limb-girdle muscular dystrophies. Hum Mol Genet. 1996 Dec;5(12):1963–1969. doi: 10.1093/hmg/5.12.1963. [DOI] [PubMed] [Google Scholar]
  23. Worton R. Muscular dystrophies: diseases of the dystrophin-glycoprotein complex. Science. 1995 Nov 3;270(5237):755–756. doi: 10.1126/science.270.5237.755. [DOI] [PubMed] [Google Scholar]

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