Abstract
We have correlated a detailed clinical assessment of 67 patients with proven Becker muscular dystrophy with the results from genetic and protein analyses. There was an overall deletion frequency of 80%, rising to 92.6% in the large group of patients defined on clinical grounds as being of “typically” mild severity. The deletions in this group were all clustered in the region of the gene between exons 45 and 59; the most common deletion was of exons 45–47 and all but one started at exon 45. No similar deletions were seen in the patients with more severe disease, in whom the diverse genetic defects included a duplication and a very large deletion. Dystrophin patterns in the “typical” group were also very characteristic, and in both groups were as predicted from the genetic defect, the size of deletions being inversely proportional to the size of the protein produced.
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Bartlett RJ, Walker AP, Laing NG, Koh J, Secore SL, Speer MC, Pericak-Vance MA, Hung WY, Yamaoka LH, Siddique T, Kandt R, Roses AD (1989) Inherited deletion of Duchenne muscular dystrophy locus in normal male. Lancet 1:496–497
Baumbach LL, Chamberlain IS, Ward PA, Farwell NJ, Caskey CT (1989) Molecular and clinical correlations of deletions leading to Duchenne and Becker muscular dystrophies. Neurology 39:465–474
Beggs AH, Koenig M, Boyce FM, Kunkel LM (1990) Detection of 98% of DMDBMD gene deletions by polymerase chain reaction. Hum Genet 86:45–48
Beggs AH, Hoffman EP, Synder JR, Arahata K, Specht L, Shapiro F, Angelini C, Sugita H, Kunkel LM (1991) Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am J Hum Genet 49:54–67
Blonden LAJ, Dunnen JT den, Paassen HMB van, Wapemaar MC, Ginjaar HB, Bakker E, Pearson PL, Ommen GJB van (1989) High resolution deletion breakpoint mapping in the DMD gene by whole cosmid hybridisation. Nucleic Acids Res 17:5611–5621
Bushby KMD (1992) Genetic and clinical correlations of Xp21 muscular dystrophy. J Inherited Metab Dis 15:551–564
Bushby KMD, Gardner-Medwin D (1992) The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. I. Natural history. J Neurol 240:98–104
Campbell KP, Kahl SD (1989) Association of dystrophin and an integral membrane glycoprotein. Nature 338:259–262
Chelly J, Gilgenkrantz H, Lambert M, Hamard G, Chafey P, Recan D, Ginjaar IB, Fardeau M, Tome F, Kahn A, Kaplan JC (1991) The dystrophin transcripts in DMD and BMD patients with gene deletion. Angelini C, Danieli GA, Fontanari D (eds) Muscular dystrophy research: from molecular diagnosis toward therapy. (Excerpta Medica international congress set 934) Excerpta Medica, Amsterdam, pp 147–156
Cross RA, Stewart M, Kendrick-Jones J (1991) Structural predictions for the central domain of dytrophin. FEBS Lett 262:87–92
Cullen MJ, Walsh J, Nicholson LVB, Harris JB (1990) Ultrastructural localisation of dystrophin in human muscle by using gold immunolabelling. Proc R Soc Lond 240:197–210
Dunnen IT den, Grootscholten PM, Bakker E, Blonden LAJ, Ginjaar HB, Wagenaar MC, Passen HMB van, Broeckhaven C van, Pearson PL, Ommen GJB van (1989) Topography of the Duchenne muscular dystrophy (DMD) gene: FIGS and cDNA analysis of 194 cases reveals 115 deletion and 13 duplications. Am J Hum Genet 45:835–847
England SB, Nicholson LVB, Johnson MA, Forrest SM, Love DR, Zubrycka-Gaarn EE, Bulman DE, Harris JB, Davies KE (1990) Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature 342:180–182
Forrest SM, Cross GS, Speer A, Gardner-Medwin D, Burn J, Davies KE (1987) Preferential deletions of exons in Duchenne and Becker muscular dystrophy. Nature 359:638–640
Gilgenkrantz H, Chelly J, Lambert M, Recan D, Barbot JC, Ommen GJB van (1989) Analysis of molecular deletions with cDNA probes in patients with Duchenne and Becker muscular dystrophies. Genomics 5:574–580
Gillard EF, Chamberlain JS, Murphy EG, Duff CL, Smith B, Burghes AHM, Thompson MW, Sutherland J, Oss I, Bodry SE, Klamut HJ, Ray PN, Worton RG (1989) Molecular and phenotypic analysis of patients with deletions within the deletion rich region of the Duchenne muscular dystrophy (DMD) gene. Am J Hum Genet 45:507–520
Gospe SM, Lozaro RP, Lava NS, Grootscholten BS, Scott MD, Fischbeck KH (1989) Familial X-linked myalgia and cramps: a non-progressive myopathy associated with a deletion in the dystrophin gene. Neurology 39:1277–1280
Hodgson S, Hart K, Abbs S, Heckmatt J, Rodillo E, Bobrow M, Dubowitz V (1989) Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. J Med Genet 26:682–693
Hoffman EP, Brown RH Jr, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928
Hoffman EP, Fischbeck KH, Brown RH Jr, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM (1988) Characterisation of dystrophin in muscle biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med 318:1363–1368
Hoffman EP, Kunkel LP, Angelini C, Clarke A, Johnson M, Harris JB (1989) Improved diagnosis of Becker muscular dystrophy by dystrophin testing. Neurology 39:1011–1017
Koenig M, Kunkel LM (1990) Detailed analysis of the repeat domains of dystrophin reveals four potential hinge segments that may confer flexibility. J Biol Chem 265:4560–4566
Koenig M, Hoffman EP, Bertelson CJ, Monaco AP, Feener C, Kunkel LM (1987) Complete cloning of the Duchenne Muscular Dystrophy (DMD) cDNA and preliminary genomic organisation of the DMD gene in normal and affected individuals. Cell 50:509–517
Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–228
Koenig M, Beggs AH, Mayer M, Scherpf S, Heindrich K, Bettecken T, Meng G, Muller CR, Lindlof M, Kaariainen H, De la Chapelle A, Kiuru A, Savontaus M-L, Gilgencrantz H, Recan D, Chelly J, Kaplan J-C, Covone AE, Archidiacono N, Romeo G, Liechti-Gallati S, Schneider V, Braga S, Moser H, Darras BT, Murhpy P, Rrancke U, Chen JD, Morgan G, Denton M, Greenberg CR, Wrongemann K, Blonden LAJ, Paassen HMB van, Ommen GJB van, Kunkel LM (1989) The molecular basis for Duchenne versus Becker dystrophy: correlation of severity with type of deletion. Am J Hum Genet 45:498–506
Lidov HGW, Byers TJ, Watkins SC, Kunkel LM (1990) Localisation of dystrophin to post-synaptic regions of central nervous system cortical neurons. Nature 348:725–728
Liechti-Gallati S, Koenig M, Kunkel LM, Frez D, Bolthauser E, Schneider V, Braza S, Moser H (1989) Molecular deletion patterns in Duchenne and Becker type muscular dystrophy. Hum Genet 81:343–348
Love DR, England SB, Speer A, Marsden RF, Bloomfield JF, Roche AL, Cross GS, Mountford RC, Smith TJ, Davies KE (1991) Sequences of junction fragments in the deletion-prone region of the dystrophin gene. Genomics 10:57–67
Medori R, Brooke MH, Waterston RH (1989) Genetic abnormalities in Duchenne and Becker dystrophies: clinical correlations. Neurology 39:461–465
Medori R, Brooke MH, Waterston RH (1989) Two dissimilar brothers with Becker's dystrophy have an idential genetic defect. Neurology 39:1493–1496
Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM (1988) An explanation for the phenotypic difference between patients bearing partial deletions of the DMD locus. Genomics 2:90–95
Nicholson LVB, Davison K, Falkous G, Harwood C, O'Donnell E, Slater CR, Harris JB (1989) Dystrophin in skeletal muscle. I. Western blot analysis using a monoclonal antibody. J Neurol Sci 94:125–136
Nicholson LVB, Johnson MA, Gardner-Medwin D, Bhattacharya SS, Harris JB (1990) Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy. Acta Neuropathol 80:239–250
Nicholson LVB, Johnson MA, Davison K, O'Donnell E, Falkous G, Barron M, Harris JB (1992) Dystrophin or a “related protein” in Duchenne muscular dystrophy? Acta Neurol Scan 86:8–14
Norman AM, Thomas NJT, Kingston HM, Harper P (1990) Becker muscular dystrophy: correlation of deletion type with clinical severity. J Med Genet 27:236–239
Passos-Bueno MR, Rapport D, Love D, Flint T, Bortolini ER, Zatz M, Davies KE (1990) Screening of deletions in the dystrophin gene with the cDNA probes Cf23a, Cf56a and Cf15a. J Med Genet 27:145–150
Rappaport D, Passos-Bueno MR, Brandao L (1991) Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy. Am J Med Genet 39:437–441
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Bushby, K.M.D., Gardner-Medwin, D., Nicholson, L.V.B. et al. The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. J Neurol 240, 105–112 (1993). https://doi.org/10.1007/BF00858726
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DOI: https://doi.org/10.1007/BF00858726