Journal of Neurology

, Volume 241, Issue 5, pp 331–334 | Cite as

A 400-kb tandem duplication within the dystrophin gene leads to severe Becker muscular dystrophy

  • R. Gold
  • W. Kreß
  • T. Bettecken
  • H. Reichmann
  • C. R. Müller
Original Communication

Abstract

We describe a family with a large duplication of exons 2–16 of the dystrophin gene. It was characterized by immunocytochemistry, field-inversion gel electrophoresis and quantitative Southern blots. Our observations are of clinical interest in that they demonstrate an intermediate disease course despite a disrupted reading frame of dystrophin as postulated from exon-intron boundaries. We discuss possible mechanisms which may explain the unusual phenotype in our patient.

Key words

Dystrophin Intragenic duplication Becker muscular dystrophy 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Angelini C, Beggs AH, Hoffman EP, et al (1990) Enormous dystrophin in a patient with Becker muscular dystrophy. Neurology 40:808–812Google Scholar
  2. 2.
    Arahata K, Ishihara T, Kamakura K, et al (1989) Mosaic expression of dystrophin in symptomatic carriers of Duchenne's muscular dystrophy. N Engl J Med 320:138–142Google Scholar
  3. 3.
    Bertelson CJ, Bartley JA, Monaco AP, et al (1986) Localisation of Xp21 meiotic exchange points in Duchenne muscular dystrophy families. J Med Genet 23:531–537Google Scholar
  4. 4.
    Bettecken T, Müller CR (1989) Identification of a 220-kb insertion into the Duchenne gene in a family with an atypical course of muscular dystrophy. Genomics 4:592–596Google Scholar
  5. 5.
    Cooper BJ (1989) Animal models of Duchenne and Becker muscular dystrophy. Br Med Bull 45:703–718Google Scholar
  6. 6.
    Den Dunnen JT, Bakker E, Klein Breteler EG, et al (1987) Direct detection of more than 50% of the Duchenne muscular dystrophy mutations by field inversion gels. Nature 329:640–642Google Scholar
  7. 7.
    Dubowitz V (1985) Muscle biopsy. A practical approach, 2nd edn. Balliere Tindall, LondonGoogle Scholar
  8. 8.
    Forrest SM, Cross GS, Speer A, et al (1987) Preferential deletion of exons in Duchenne and Becker muscular dystrophies. Nature 329:638–640Google Scholar
  9. 9.
    Gangopadhyay SB, Sheratt TG, Heckmatt JZ, et al (1992) Dystrophin in frameshift deletion patients with Becker muscular dystrophy. Am J Hum Genet 51:562–570Google Scholar
  10. 10.
    Gold R, Meurers B, Kreß W, Müller CR, Reichmann H (1990) Duchenne muscular dystrophy: evidence for somatic reversion of the mutation in man. J Neurol 237:494–495Google Scholar
  11. 11.
    Gold R, Kreß W, Meurers B et al. (1992) Becker muscular dystrophy: detection of unusual disease courses by combined approach to dystrophin analysis. Muscle Nerve 15:214–218Google Scholar
  12. 12.
    Hoffman EP, Brown RH, Kunkel LM (1987) Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51:919–928Google Scholar
  13. 13.
    Hoffman EP, Morgan JE, Watkins SC, et al (1990) Somatic reversion/suppression of the mouse mdx phenotype in vivo. J Neurol Sci 99:9–25Google Scholar
  14. 14.
    Hu X, Burghes AH, Ray PN, Thompson MW, et al (1988) Partial gene duplications in Duchenne and Becker muscular dystrophies. J Med Genet 25:369–376Google Scholar
  15. 15.
    Hu X, Ray PN, Murphy EG, et al (1990) Duplicational mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin and phenotype/genotype correlation. Am J Hum Genet 46:682–695Google Scholar
  16. 16.
    Klein CJ, Coovert DC, Bulman DE, et al (1992) Somatic reversion/suppression in Duchenne muscular dystrophy (DMD): evidence supporting a framerestoring mechanism in rare dystrophin-positive fibres. Am J Hum Genet 50:950–959Google Scholar
  17. 17.
    König 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 45:498–506Google Scholar
  18. 18.
    Malhotra SB, Haart KA, Klamut HJ, et al (1988) Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science 242:755–759Google Scholar
  19. 19.
    Roberts RG, Coffey AJ, Bobrow M, Bentley DR (1993) Exon structure of the human dystrophin gene. Genomics 16:536–538Google Scholar
  20. 20.
    Winter RM, Pembrey ME (1982) Does unequal crossing-over contribute to the mutation rate in Duchenne muscular dystrophy? Am J Med Genet 12:437–441Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • R. Gold
    • 1
  • W. Kreß
    • 2
  • T. Bettecken
    • 2
  • H. Reichmann
    • 1
  • C. R. Müller
    • 2
  1. 1.Department of NeurologyUniversität WürzburgWürzburgGermany
  2. 2.C. R. Müller Universität WürzburgWürzburgGermany

Personalised recommendations