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Journal List > Am J Hum Genet > v.45(4); Oct 1989

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Am J Hum Genet. 1989 October; 45(4): 498–506.
PMCID: PMC1683519
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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, and L. M. Kunkel
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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.
  • Baumbach LL, Chamberlain JS, Ward PA, Farwell NJ, Caskey CT. Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology. 1989 Apr;39(4):465–474. [PubMed]
  • Burghes AH, Logan C, Hu X, Belfall B, Worton RG, Ray PN. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. Nature. 328(6129):434–437. [PubMed]
  • Burmeister M, Monaco AP, Gillard EF, van Ommen GJ, Affara NA, Ferguson-Smith MA, Kunkel LM, Lehrach H. A 10-megabase physical map of human Xp21, including the Duchenne muscular dystrophy gene. Genomics. 1988 Apr;2(3):189–202. [PubMed]
  • Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. 1988 Dec 9;16(23):11141–11156. [PubMed]
  • Darras BT, Blattner P, Harper JF, Spiro AJ, 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. [PubMed]
  • Darras BT, 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. [PubMed]
  • Forrest SM, Smith TJ, Cross GS, Read AP, Thomas NS, Mountford RC, Harper PS, Geirsson RT, Davies KE. Effective strategy for prenatal prediction of Duchenne and Becker muscular dystrophy. Lancet. 1987 Dec 5;2(8571):1294–1297. [PubMed]
  • Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, et al. 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. [PubMed]
  • Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM. 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. [PubMed]
  • Koenig M, Monaco AP, Kunkel LM. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell. 1988 Apr 22;53(2):219–228. [PubMed]
  • Lemaire C, Heilig R, Mandel JL. 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. [PubMed]
  • Liechti-Gallati S, Koenig M, Kunkel LM, 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. [PubMed]
  • Lindlöf M, Kiuru A, Kääriäinen H, Kalimo H, Lang H, Pihko H, Rapola J, Somer H, Somer M, Savontaus ML, et al. Gene deletions in X-linked muscular dystrophy. Am J Hum Genet. 1989 Apr;44(4):496–503. [PubMed]
  • McCabe ER, Towbin J, Chamberlain J, Baumbach L, Witkowski J, van Ommen GJ, Koenig M, Kunkel LM, Seltzer WK. 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. [PubMed]
  • Malhotra SB, Hart KA, Klamut HJ, Thomas NS, Bodrug SE, Burghes AH, Bobrow M, Harper PS, Thompson MW, Ray PN, et al. Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science. 1988 Nov 4;242(4879):755–759. [PubMed]
  • Monaco AP, Bertelson CJ, Colletti-Feener C, Kunkel LM. Localization and cloning of Xp21 deletion breakpoints involved in muscular dystrophy. Hum Genet. 1987 Mar;75(3):221–227. [PubMed]
  • Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics. 1988 Jan;2(1):90–95. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • van Ommen GJ, Bertelson C, Ginjaar HB, den Dunnen JT, Bakker E, Chelly J, Matton M, van Essen AJ, Bartley J, Kunkel LM, et al. 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. [PubMed]
  • Wapenaar MC, Kievits T, Hart KA, Abbs S, Blonden LA, den Dunnen JT, Grootscholten PM, Bakker E, Verellen-Dumoulin C, Bobrow M, et al. A deletion hot spot in the Duchenne muscular dystrophy gene. Genomics. 1988 Feb;2(2):101–108. [PubMed]
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