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. 1989 Oct;45(4):498–506.

The molecular basis for Duchenne versus Becker muscular dystrophy: Correlation of severity with type of deletion

M Koenig, A H Beggs, M Moyer, S Scherpf, K Heindrich, T Bettecken, G Meng, C R Müller, M Lindlöf, H Kaariainen, A de la Chapelle, A Kiuru, M-L Savontaus, H Gilgenkrantz, D Récan, J Chelly, J-C Kaplan, A E Covone, N Archidiacono, G Romeo, S Liechti-Gallati, V Schneider, S Braga, H Moser, B T Darras, P Murphy, U Francke, J D Chen, G Morgan, M Denton, C R Greenberg, K Wrogemann, L A J Blonden, H M B van Paassen, G J B van Ommen, L M Kunkel
PMCID: PMC1683519  PMID: 2491009

Abstract

About 60% of both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) is due to deletions of the dystrophin gene. For cases with a deletion mutation, the “reading frame” hypothesis predicts that BMD patients produce a semifunctional, internally deleted dystrophin protein, whereas DMD patients produce a severely truncated protein that would be unstable. To test the validity of this theory, we analyzed 258 independent deletions at the DMD/BMD locus. The correlation between phenotype and type of deletion mutation is in agreement with the “reading frame” theory in 92% of cases and is of diagnostic and prognostic significance. The distribution and frequency of deletions spanning the entire locus suggests that many “in-frame” deletions of the dystrophin gene are not detected because the individuals bearing them are either asymptomatic or exhibit non-DMD/non-BMD clinical features.

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Selected References

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

  1. Baumbach L. L., Chamberlain J. S., Ward P. A., Farwell N. J., Caskey C. T. Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology. 1989 Apr;39(4):465–474. doi: 10.1212/wnl.39.4.465. [DOI] [PubMed] [Google Scholar]
  2. Burghes A. H., Logan C., Hu X., Belfall B., Worton R. G., Ray P. N. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. 1987 Jul 30-Aug 5Nature. 328(6129):434–437. doi: 10.1038/328434a0. [DOI] [PubMed] [Google Scholar]
  3. Burmeister M., Monaco A. P., Gillard E. F., van Ommen G. J., Affara N. A., Ferguson-Smith M. A., Kunkel L. M., Lehrach H. A 10-megabase physical map of human Xp21, including the Duchenne muscular dystrophy gene. Genomics. 1988 Apr;2(3):189–202. doi: 10.1016/0888-7543(88)90002-x. [DOI] [PubMed] [Google Scholar]
  4. Chamberlain J. S., Gibbs R. A., Ranier J. E., Nguyen P. N., Caskey C. T. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. 1988 Dec 9;16(23):11141–11156. doi: 10.1093/nar/16.23.11141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Darras B. T., Blattner P., Harper J. F., Spiro A. J., Alter S., Francke U. Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on HindIII and BglII exon-containing fragment maps, meiotic and mitotic origin of the mutations. Am J Hum Genet. 1988 Nov;43(5):620–629. [PMC free article] [PubMed] [Google Scholar]
  6. Darras B. T., Francke U. Myopathy in complex glycerol kinase deficiency patients is due to 3' deletions of the dystrophin gene. Am J Hum Genet. 1988 Aug;43(2):126–130. [PMC free article] [PubMed] [Google Scholar]
  7. Forrest S. M., Smith T. J., Cross G. S., Read A. P., Thomas N. S., Mountford R. C., Harper P. S., Geirsson R. T., Davies K. E. Effective strategy for prenatal prediction of Duchenne and Becker muscular dystrophy. Lancet. 1987 Dec 5;2(8571):1294–1297. doi: 10.1016/s0140-6736(87)91192-5. [DOI] [PubMed] [Google Scholar]
  8. Hoffman E. P., Fischbeck K. H., Brown R. H., Johnson M., Medori R., Loike J. D., Harris J. B., Waterston R., Brooke M., Specht L. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med. 1988 May 26;318(21):1363–1368. doi: 10.1056/NEJM198805263182104. [DOI] [PubMed] [Google Scholar]
  9. Koenig M., Hoffman E. P., Bertelson C. J., Monaco A. P., Feener C., Kunkel L. M. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell. 1987 Jul 31;50(3):509–517. doi: 10.1016/0092-8674(87)90504-6. [DOI] [PubMed] [Google Scholar]
  10. Koenig M., Monaco A. P., Kunkel L. M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219–228. doi: 10.1016/0092-8674(88)90383-2. [DOI] [PubMed] [Google Scholar]
  11. Lemaire C., Heilig R., Mandel J. L. The chicken dystrophin cDNA: striking conservation of the C-terminal coding and 3' untranslated regions between man and chicken. EMBO J. 1988 Dec 20;7(13):4157–4162. doi: 10.1002/j.1460-2075.1988.tb03311.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Liechti-Gallati S., Koenig M., Kunkel L. M., Frey D., Boltshauser E., Schneider V., Braga S., Moser H. Molecular deletion patterns in Duchenne and Becker type muscular dystrophy. Hum Genet. 1989 Mar;81(4):343–348. doi: 10.1007/BF00283688. [DOI] [PubMed] [Google Scholar]
  13. Lindlöf M., Kiuru A., Käriäinen H., Kalimo H., Lang H., Pihko H., Rapola J., Somer H., Somer M., Savontaus M. L. Gene deletions in X-linked muscular dystrophy. Am J Hum Genet. 1989 Apr;44(4):496–503. [PMC free article] [PubMed] [Google Scholar]
  14. Malhotra S. B., Hart K. A., Klamut H. J., Thomas N. S., Bodrug S. E., Burghes A. H., Bobrow M., Harper P. S., Thompson M. W., Ray P. N. Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science. 1988 Nov 4;242(4879):755–759. doi: 10.1126/science.3055295. [DOI] [PubMed] [Google Scholar]
  15. McCabe E. R., Towbin J., Chamberlain J., Baumbach L., Witkowski J., van Ommen G. J., Koenig M., Kunkel L. M., Seltzer W. K. Complementary DNA probes for the Duchenne muscular dystrophy locus demonstrate a previously undetectable deletion in a patient with dystrophic myopathy, glycerol kinase deficiency, and congenital adrenal hypoplasia. J Clin Invest. 1989 Jan;83(1):95–99. doi: 10.1172/JCI113890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Monaco A. P., Bertelson C. J., Colletti-Feener C., Kunkel L. M. Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. Hum Genet. 1987 Mar;75(3):221–227. doi: 10.1007/BF00281063. [DOI] [PubMed] [Google Scholar]
  17. Monaco A. P., Bertelson C. J., Liechti-Gallati S., Moser H., Kunkel L. M. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics. 1988 Jan;2(1):90–95. doi: 10.1016/0888-7543(88)90113-9. [DOI] [PubMed] [Google Scholar]
  18. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  19. Wapenaar M. C., Kievits T., Hart K. A., Abbs S., Blonden L. A., den Dunnen J. T., Grootscholten P. M., Bakker E., Verellen-Dumoulin C., Bobrow M. A deletion hot spot in the Duchenne muscular dystrophy gene. Genomics. 1988 Feb;2(2):101–108. doi: 10.1016/0888-7543(88)90090-0. [DOI] [PubMed] [Google Scholar]
  20. van Ommen G. J., Bertelson C., Ginjaar H. B., den Dunnen J. T., Bakker E., Chelly J., Matton M., van Essen A. J., Bartley J., Kunkel L. M. Long-range genomic map of the Duchenne muscular dystrophy (DMD) gene: isolation and use of J66 (DXS268), a distal intragenic marker. Genomics. 1987 Dec;1(4):329–336. doi: 10.1016/0888-7543(87)90032-2. [DOI] [PubMed] [Google Scholar]

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