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. 1996 Dec;33(12):1027–1031. doi: 10.1136/jmg.33.12.1027

Identification of carriers of Duchenne/Becker muscular dystrophy by a novel method based on detection of junction fragments in the dystrophin gene.

H Yamagishi 1, S Kato 1, Y Hiraishi 1, T Ishihara 1, J Hata 1, N Matsuo 1, T Takano 1
PMCID: PMC1050816  PMID: 9004137

Abstract

We developed a Southern blotting based method that uses rare cutting restriction endonucleases and electrophoresis of single stranded DNA to detect junction fragments resulting from the rearranged dystrophin gene. By conventional Southern blot hybridisation, no junction fragments were detected in 27 unrelated patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy, who had 20 deletions and seven duplications in the dystrophin gene. With our new method, junction fragments were detected in 21 of these 27 patients. When the junction fragments were used as markers, five carriers were unequivocally diagnosed among six females from two families of DMD/ BMD patients. This novel method allows simple and definitive identification of carriers with risk factors for DMD/BMD without using quantitative Southern blot hybridisation.

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Selected References

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

  1. Beggs A. H., Koenig M., Boyce F. M., Kunkel L. M. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet. 1990 Nov;86(1):45–48. doi: 10.1007/BF00205170. [DOI] [PubMed] [Google Scholar]
  2. Blonden L. A., Grootscholten P. M., den Dunnen J. T., Bakker E., Abbs S., Bobrow M., Boehm C., van Broeckhoven C., Baumbach L., Chamberlain J. 242 breakpoints in the 200-kb deletion-prone P20 region of the DMD gene are widely spread. Genomics. 1991 Jul;10(3):631–639. doi: 10.1016/0888-7543(91)90445-k. [DOI] [PubMed] [Google Scholar]
  3. Blonden L. A., den Dunnen J. T., van Paassen H. M., Wapenaar M. C., Grootscholten P. M., Ginjaar H. B., Bakker E., Pearson P. L., van Ommen G. J. High resolution deletion breakpoint mapping in the DMD gene by whole cosmid hybridization. Nucleic Acids Res. 1989 Jul 25;17(14):5611–5621. doi: 10.1093/nar/17.14.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Den Dunnen J. T., Grootscholten P. M., Bakker E., Blonden L. A., Ginjaar H. B., Wapenaar M. C., van Paassen H. M., van Broeckhoven C., Pearson P. L., van Ommen G. J. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am J Hum Genet. 1989 Dec;45(6):835–847. [PMC free article] [PubMed] [Google Scholar]
  6. Gillard E. F., Chamberlain J. S., Murphy E. G., Duff C. L., Smith B., Burghes A. H., Thompson M. W., Sutherland J., Oss I., Bodrug S. E. Molecular and phenotypic analysis of patients with deletions within the deletion-rich region of the Duchenne muscular dystrophy (DMD) gene. Am J Hum Genet. 1989 Oct;45(4):507–520. [PMC free article] [PubMed] [Google Scholar]
  7. Herrmann B. G., Frischauf A. M. Isolation of genomic DNA. Methods Enzymol. 1987;152:180–183. doi: 10.1016/0076-6879(87)52018-3. [DOI] [PubMed] [Google Scholar]
  8. Hiraishi Y., Kato S., Ishihara T., Takano T. Quantitative Southern blot analysis in the dystrophin gene of Japanese patients with Duchenne or Becker muscular dystrophy: a high frequency of duplications. J Med Genet. 1992 Dec;29(12):897–901. doi: 10.1136/jmg.29.12.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hu X. Y., Burghes A. H., Ray P. N., Thompson M. W., Murphy E. G., Worton R. G. Partial gene duplication in Duchenne and Becker muscular dystrophies. J Med Genet. 1988 Jun;25(6):369–376. doi: 10.1136/jmg.25.6.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hu X. Y., Ray P. N., Murphy E. G., Thompson M. W., Worton R. G. Duplicational mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin, and phenotypegenotype correlation. Am J Hum Genet. 1990 Apr;46(4):682–695. [PMC free article] [PubMed] [Google Scholar]
  11. Kato S., Tachibana K., Takayama N., Kataoka H., Yoshida M. C., Takano T. Genetic recombination in a chromosomal translocation t(2;8)(p11;q24) of a Burkitt's lymphoma cell line, KOBK101. Gene. 1991 Jan 15;97(2):239–244. doi: 10.1016/0378-1119(91)90057-i. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Lau Y. L., Srivastava G., Wong V., Liu Y. T., Ho F. C., Yeung C. Y. Deletions, duplications and novel restriction fragment length polymorphism in Duchenne and Becker muscular dystrophies. Clin Genet. 1992 May;41(5):252–258. doi: 10.1111/j.1399-0004.1992.tb03676.x. [DOI] [PubMed] [Google Scholar]
  14. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Niemann-Seyde S., Slomski R., Rininsland F., Ellermeyer U., Kwiatkowska J., Reiss J. Molecular genetic analysis of 67 patients with Duchenne/Becker muscular dystrophy. Hum Genet. 1992 Sep-Oct;90(1-2):65–70. doi: 10.1007/BF00210746. [DOI] [PubMed] [Google Scholar]
  16. Roberts R. G., Coffey A. J., Bobrow M., Bentley D. R. Exon structure of the human dystrophin gene. Genomics. 1993 May;16(2):536–538. doi: 10.1006/geno.1993.1225. [DOI] [PubMed] [Google Scholar]
  17. Schwartz L. S., Tarleton J., Popovich B., Seltzer W. K., Hoffman E. P. Fluorescent multiplex linkage analysis and carrier detection for Duchenne/Becker muscular dystrophy. Am J Hum Genet. 1992 Oct;51(4):721–729. [PMC free article] [PubMed] [Google Scholar]
  18. Worton R. G., Thompson M. W. Genetics of Duchenne muscular dystrophy. Annu Rev Genet. 1988;22:601–629. doi: 10.1146/annurev.ge.22.120188.003125. [DOI] [PubMed] [Google Scholar]
  19. Yau S. C., Bobrow M., Mathew C. G., Abbs S. J. Accurate diagnosis of carriers of deletions and duplications in Duchenne/Becker muscular dystrophy by fluorescent dosage analysis. J Med Genet. 1996 Jul;33(7):550–558. doi: 10.1136/jmg.33.7.550. [DOI] [PMC free article] [PubMed] [Google Scholar]

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