Skip to main content
NCBI home page
American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1996 Nov;59(5):1040–1047.

Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation.

E M McNally 1, M R Passos-Bueno 1, C G Bönnemann 1, M Vainzof 1, E de Sá Moreira 1, H G Lidov 1, K B Othmane 1, P H Denton 1, J M Vance 1, M Zatz 1, L M Kunkel 1
PMCID: PMC1914841  PMID: 8900232

Abstract

Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein gamma-sarcoglycan. The previous mutation analysis of gamma-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the gamma-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding gamma-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the gamma-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of alpha-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the gamma-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from gamma-sarcoglycan gene mutations.

Full text

PDF
1040

Images in this article

1042Figure 2
on p.1042
1045Figure 5
on p.1045

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ben Hamida M., Fardeau M., Attia N. Severe childhood muscular dystrophy affecting both sexes and frequent in Tunisia. Muscle Nerve. 1983 Sep;6(7):469–480. doi: 10.1002/mus.880060702. [DOI] [PubMed] [Google Scholar]
  2. Ben Othmane K., Ben Hamida M., Pericak-Vance M. A., Ben Hamida C., Blel S., Carter S. C., Bowcock A. M., Petruhkin K., Gilliam T. C., Roses A. D. Linkage of Tunisian autosomal recessive Duchenne-like muscular dystrophy to the pericentromeric region of chromosome 13q. Nat Genet. 1992 Dec;2(4):315–317. doi: 10.1038/ng1292-315. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Bueno M. R., Moreira E. S., Vainzof M., Chamberlain J., Marie S. K., Pereira L., Akiyama J., Roberds S. L., Campbell K. P., Zatz M. A common missense mutation in the adhalin gene in three unrelated Brazilian families with a relatively mild form of autosomal recessive limb-girdle muscular dystrophy. Hum Mol Genet. 1995 Jul;4(7):1163–1167. doi: 10.1093/hmg/4.7.1163. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Kawai H., Akaike M., Endo T., Adachi K., Inui T., Mitsui T., Kashiwagi S., Fujiwara T., Okuno S., Shin S. Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency. J Clin Invest. 1995 Sep;96(3):1202–1207. doi: 10.1172/JCI118152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lien L. L., Feener C. A., Fischbach N., Kunkel L. M. Cloning of human microtubule-associated protein 1B and the identification of a related gene on chromosome 15. Genomics. 1994 Jul 15;22(2):273–280. doi: 10.1006/geno.1994.1384. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Ljunggren A., Duggan D., McNally E., Boylan K. B., Gama C. H., Kunkel L. M., Hoffman E. P. Primary adhalin deficiency as a cause of muscular dystrophy in patients with normal dystrophin. Ann Neurol. 1995 Sep;38(3):367–372. doi: 10.1002/ana.410380305. [DOI] [PubMed] [Google Scholar]
  11. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Monaco A. P., Neve R. L., Colletti-Feener C., Bertelson C. J., Kurnit D. M., Kunkel L. M. Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature. 1986 Oct 16;323(6089):646–650. doi: 10.1038/323646a0. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Passos-Bueno M. R., Moreira E. S., Marie S. K., Bashir R., Vasquez L., Love D. R., Vainzof M., Iughetti P., Oliveira J. R., Bakker E. Main clinical features of the three mapped autosomal recessive limb-girdle muscular dystrophies and estimated proportion of each form in 13 Brazilian families. J Med Genet. 1996 Feb;33(2):97–102. doi: 10.1136/jmg.33.2.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Vainzof M., Zubrzycka-Gaarn E. E., Rapaport D., Passos-Bueno M. R., Pavanello R. C., Pavanello-Filho I., Zatz M. Immunofluorescence dystrophin study in Duchenne dystrophy through the concomitant use of two antibodies directed against the carboxy-terminal and the amino-terminal region of the protein. J Neurol Sci. 1991 Feb;101(2):141–147. doi: 10.1016/0022-510x(91)90038-9. [DOI] [PubMed] [Google Scholar]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

RESOURCES