Journal of Inherited Metabolic Disease

, Volume 15, Issue 4, pp 551–564

Genetic and clinical correlations of Xp21 muscular dystrophy

  • K. M. D. Bushby
The X Chromosome


We have investigated over 100 patients with Xp21 muscular dystrophy, drawing together the results of detailed clinical, genetic and dystrophin investigations. A spectrum of disease severity was confirmed, with the most homogeneous clinical groups being at either end of the spectrum, represented by the typical Duchenne and Becker phenotypes. The groups in between showed clinical heterogeneity, and variability in the genetic and dystrophin results. While an out-of-frame deletion in association with undetectable dystrophin is most likely to predict the most severe phenotype, and increasing abundance of dystrophin is associated generally with a milder clinical course, no value of dystrophin abundance reliably predicts a particular phenotype. However, deletions of the dystrophin gene involving exons 45–47 and 45–48 especially do seem to be consistently associated with the mildest Becker phenotype. Additional factors must play a role in determining the exact clinical course.


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  1. Becker PE (1962) Two new families of benign sex-linked recessive muscular dystrophy.Rev Can Biol 21: 551–566.Google Scholar
  2. Becker PE, Kiener F (1955) Eine neue X-chromosome muskeldystrophie.Arch Psychiatr Z Neurol 193: 427–448.Google Scholar
  3. Boyce FM, Beggs AH, Feener C, Kunkel LM (1991) Dystrophin is transcribed in brain from a distant upstream promoter.Proc Natl Acad Sci USA 88: 1276–1280.Google Scholar
  4. Brooke MH, Fenichel GM, Griggs RC et al (1983) Clinical investigation in Duchenne dystrophy: 2. Determination of the ‘power’ of therapeutic trials based on the natural history.Muscle Nerve 6: 91–103.Google Scholar
  5. Bulman DE, Gangopadhyay SB, Bebchuck KG, Worton RG, Ray PN (1991) Point mutation in the human dystrophin gene: identification through western blot analysis.Genomics 10: 457–460.Google Scholar
  6. Bushby KMD, Gardner-Medwin D (1992) The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. 1: Natural history.J Neurol (in press).Google Scholar
  7. Bushby KMD, Thambyayah M, Gardner-Medwin D (1991) Prevalence and incidence of Becker muscular dystrophy.Lancet 338: 1022–1024.Google Scholar
  8. Bushby KMD, Gardner-Medwin D, Nicholson LVB, et al (1992) The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. 2: Correlation of phenotype with genetic and protein abnormalities.J. Neurol (in press).Google Scholar
  9. Campbell KP, Kahl SD (1989) Association of dystrophin and an integral membrane glycoprotein.Nature 338: 259–262.Google Scholar
  10. Chelly J, Hamard G, Koulakoff A, Kaplan J-C, Kahn A, Berwald-Netter Y (1990) Dystrophin gene transcribed from different promoters in neuronal and glial cells.Nature 344: 64–65.Google Scholar
  11. Chelly J, Gilgenkrantz H, Lambert M et al (1991) The dystrophin transcripts in DMD and BMD patients with gene deletion. In Angelini C, Danieli GA, Fontanari D, eds.Muscular Dystrophy Research: From Molecular Diagnosis Toward Therapy. Amsterdam: Excerpta Medica, 147–156.Google Scholar
  12. Clarke A, Davies KKE, Gardner-Medwin D, Burn J, Hudgson P (1989) Xp21 DNA probe in diagnosis of muscular dystrophy and spinal muscular atrophy.Lancet 1: 443.Google Scholar
  13. Cornelio F, Dworzak F, Morandi L, Fedrizzi E, Balestrini MR, Gondori L (1982) Functional evaluation of DMD: proposal for a protocol.Ital J Neurol Sci 3(4): 323–330.Google Scholar
  14. Emery AEH (1988)Duchenne Muscular Dystrophy. Revised edition. Oxford: Oxford University Press.Google Scholar
  15. Emery AEH, Skinner R (1976) Clinical studies in benign (Becker-type) X-linked muscular dystrophy.Clin Genet 10: 189–201.Google Scholar
  16. Gardner-Medwin D, Sharples P (1989) Some studies of the Duchenne and autosomal recessive types of muscular dystrophy.Brain Dev 2: 91–97.Google Scholar
  17. Gospe SM, Lazaro RP, Lava NS, Grootscholten PM, Scott AB, 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.Google Scholar
  18. Hu X, Ray PN, Murphy EG, Thompson MW, Worton RG (1990) Duplication mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin, and phenotype-genotype correlation.Am J Hum Genet 46: 682–695.Google Scholar
  19. Kingston HM, Sarfarazi M, Thomas NST, Harper PS (1984) Localisation of the Becker muscular dystrophy gene on the short arm of the X chromosome by linkage to cloned DNA sequences.Hum Genet 67: 6–17.Google Scholar
  20. 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.Google Scholar
  21. Koenig M, Beggs AH, Moyer M et al (1989) The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion.Am J Hum Genet 45: 498–506.Google Scholar
  22. Malhotra SB, Hart KA, Klamut HJ et al (1988) Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy.Science 242: 755–759.Google Scholar
  23. Monaco AP, Bertelson CJ, Liechti-Gallati S, Moser H, Kunkel LM (1988) An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus.Genomics 2: 90–95.Google Scholar
  24. Moser H, Emery AEH (1974) The manifesting carrier in Duchenne muscular dystrophy.Clin Genet 5: 271–284.Google Scholar
  25. Nicholson LVB, Davison K, Falkous G et al (1989) Dystrophin in skeletal muscle: I. Western blot analysis using a monoclonal antibody.J Neurol Sci 94: 125–136.Google Scholar
  26. Nicholson LVB, Johnson MA, Gardner-Medwin D, Bhattacharya S, Harris JB (1990) Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy.Acta Neuropathol 80: 239–250.Google Scholar
  27. Nicholson LVB, Johnson MA, Davison K et al (1991) Patterns of dystrophin labelling in muscle from patients with Duchenne and Becker muscular dystrophy. In Angelini C, Danieli GA, Fontanari D, eds.Muscular Dystrophy Research: From Molecular Diagnosis Toward Therapy. Amsterdam: Excerpta Medica, 240–241.Google Scholar
  28. Nicholson LVB, Johnson MA, Davison K et al (1992) Dystrophin or a ‘related protein’ in Duchenne muscular dystrophy?Acta Neurol Scand (in press).Google Scholar
  29. Norman A, Thomas N, Coackley J, Harper P (1989) Distinction of Becker from limb-girdle muscular dystrophy by means of dystrophin cDNA probes.Lancet 1, 466–468.Google Scholar
  30. Norman AM, Thomas NST, Kingston HM, Harper PS (1990) Becker muscular dystrophy: correlation of deletion type with clinical severity.J Med Genet 27: 236–239.Google Scholar
  31. Rapaport D, Passos-Bueno MR, Brandao L, Love DR, Vainzof M, Zatz M (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.Google Scholar
  32. Roberts RG, Barby TFM, Manners E, Bobrow M, Bentley DR (1991) Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes.Am J Hum Genet 49: 298–310.Google Scholar
  33. Shimizu T, Matsumura K, Hashimoto K et al (1988) A monoclonal antibody against a synthetic polypeptide fragment of dystrophin (amino acid sequence from position 215 to 264).Proc Japan Acad 64B: 205–208.Google Scholar
  34. Smith RA, Sibert JR, Harper PS (1990) Early development of boys with Duchenne muscular dystrophy.Dev Med Child Neurol 32: 519–527.Google Scholar
  35. Sunohara N, Arahata K, Hoffman EP et al (1990) Quadriceps myopathy: forme fruste of Becker muscular dystrophy.Ann Neurol 28: 634–639.Google Scholar
  36. Swinyard CA, Deaver GG, Greenspan L (1957) Variants of functional ability of importance in rehabilitation of patients with progressive muscular and neuromuscular diseases.Arch Phys Med Rehabil 38: 574–579.Google Scholar
  37. Vainzof M, Pavanello RCM, Filho IP et al (1990) Dystrophin immunostaining in muscles from patients with different types of muscular dystrophy: a Brazilian study.J Neurol Sci 98: 221–233.Google Scholar
  38. Vignos PJ, Spencer GE, Archibald KC (1963) Management of progressive muscular dystrophy of childhood.J Am Med Assoc 184: 89–96.Google Scholar
  39. Walton J, Gardner-Medwin D (1988) The muscular dystrophies. In Walton J, ed.Disorders of Voluntary Muscle, 5th edn. Edinburgh: Churchill Livingstone, 519–568.Google Scholar
  40. Weschler D (1974)Manual for the Weschler Intelligence Scale for Children (revised). New York: The Psychological Corporation.Google Scholar
  41. Worton RG, Thompson MW (1988) Genetics of Duchenne muscular dystrophy.Annu Rev Genet 22: 601–629.Google Scholar

Copyright information

© SSIEM and Kluwer Academic Publishers 1992

Authors and Affiliations

  • K. M. D. Bushby
    • 1
  1. 1.Department of Human GeneticsUniversity of Newcastle upon TyneNewcastle upon TyneUK

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