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. 1989 Sep;26(9):565–571. doi: 10.1136/jmg.26.9.565

Duchenne muscular dystrophy in Wales: impact of DNA linkage analysis and cDNA deletion screening.

A M Norman 1, M Upadhyaya 1, N S Thomas 1, K Roberts 1, P S Harper 1
PMCID: PMC1015695  PMID: 2810340

Abstract

A register of families with Duchenne muscular dystrophy (DMD) has been maintained in Wales since 1973. Since 1986 we have attempted to refine carrier status, and when necessary offer prenatal diagnosis, for those at significant risk by using intragenic probes. cDNA probes were included from the beginning of 1988. Thirty-four (30%) of the 115 women tested were assigned a risk of carrying the DMD gene of less than 5%. Thirty-three (29%) of the women at 5% or greater risk are now able to have prenatal diagnosis using a molecular deletion; such deletions were detected in 50% of affected boys. The remaining women could have prenatal diagnosis using a linked intragenic probe with an error rate varying between 0.25% and 9%. In 19 cases DNA samples from DMD boys who were dead at the time of analysis were used, indicating that it is essential to bank DNA from all males affected by DMD. We conclude that a large proportion of women at risk of carrying the DMD gene can now be helped by DNA studies.

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Selected References

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

  1. Bakker E., Bonten E. J., De Lange L. F., Veenema H., Majoor-Krakauer D., Hofker M. H., Van Ommen G. J., Pearson P. L. DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure. J Med Genet. 1986 Dec;23(6):573–580. doi: 10.1136/jmg.23.6.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown C. S., Thomas N. S., Sarfarazi M., Davies K. E., Kunkel L., Pearson P. L., Kingston H. M., Shaw D. J., Harper P. S. Genetic linkage relationships of seven DNA probes with Duchenne and Becker muscular dystrophy. Hum Genet. 1985;71(1):62–74. doi: 10.1007/BF00295671. [DOI] [PubMed] [Google Scholar]
  3. Burghes A. H., Logan C., Hu X., Belfall B., Worton R. G., Ray P. N. A cDNA clone from the Duchenne/Becker muscular dystrophy gene. 1987 Jul 30-Aug 5Nature. 328(6129):434–437. doi: 10.1038/328434a0. [DOI] [PubMed] [Google Scholar]
  4. Cole C. G., Walker A., Coyne A., Johnson L., Hart K. A., Hodgson S., Sheridan R., Bobrow M. Prenatal testing for Duchenne and Becker muscular dystrophy. Lancet. 1988 Feb 6;1(8580):262–266. doi: 10.1016/s0140-6736(88)90349-2. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Darras B. T., Harper J. F., Francke U. Prenatal diagnosis and detection of carriers with DNA probes in Duchenne's muscular dystrophy. N Engl J Med. 1987 Apr 16;316(16):985–992. doi: 10.1056/NEJM198704163161604. [DOI] [PubMed] [Google Scholar]
  7. Edwards J. H. The population genetics of Duchenne: natural and artificial selection in Duchenne muscular dystrophy. J Med Genet. 1986 Dec;23(6):521–530. doi: 10.1136/jmg.23.6.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Forrest S. M., Cross G. S., Speer A., Gardner-Medwin D., Burn J., Davies K. E. Preferential deletion of exons in Duchenne and Becker muscular dystrophies. Nature. 1987 Oct 15;329(6140):638–640. doi: 10.1038/329638a0. [DOI] [PubMed] [Google Scholar]
  10. Forrest S. M., Smith T. J., Cross G. S., Read A. P., Thomas N. S., Mountford R. C., Harper P. S., Geirsson R. T., Davies K. E. Effective strategy for prenatal prediction of Duchenne and Becker muscular dystrophy. Lancet. 1987 Dec 5;2(8571):1294–1297. doi: 10.1016/s0140-6736(87)91192-5. [DOI] [PubMed] [Google Scholar]
  11. Goodship J., Malcolm S., Robertson M. E., Pembrey M. E. Service experience using DNA analysis for genetic prediction in Duchenne muscular dystrophy. J Med Genet. 1988 Jan;25(1):14–19. doi: 10.1136/jmg.25.1.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hodgson S., Walker A., Cole C., Hart K., Johnson L., Heckmatt J., Dubowitz V., Bobrow M. The application of linkage analysis to genetic counselling in families with Duchenne or Becker muscular dystrophy. J Med Genet. 1987 Mar;24(3):152–159. doi: 10.1136/jmg.24.3.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Lathrop G. M., Lalouel J. M., Julier C., Ott J. Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3443–3446. doi: 10.1073/pnas.81.11.3443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Meredith A. L., Upadhyaya M., Harper P. S. Molecular genetics in clinical practice: evolution of a DNA diagnostic service. BMJ. 1988 Oct 1;297(6652):843–846. doi: 10.1136/bmj.297.6652.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Monaco A. P., Bertelson C. J., Middlesworth W., Colletti C. A., Aldridge J., Fischbeck K. H., Bartlett R., Pericak-Vance M. A., Roses A. D., Kunkel L. M. Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. 1985 Aug 29-Sep 4Nature. 316(6031):842–845. doi: 10.1038/316842a0. [DOI] [PubMed] [Google Scholar]
  17. Murray J. M., Davies K. E., Harper P. S., Meredith L., Mueller C. R., Williamson R. Linkage relationship of a cloned DNA sequence on the short arm of the X chromosome to Duchenne muscular dystrophy. Nature. 1982 Nov 4;300(5887):69–71. doi: 10.1038/300069a0. [DOI] [PubMed] [Google Scholar]
  18. Norman A. M., Rogers C., Sibert J. R., Harper P. S. Duchenne muscular dystrophy in Wales: a 15 year study, 1971 to 1986. J Med Genet. 1989 Sep;26(9):560–564. doi: 10.1136/jmg.26.9.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Old J. M., Davies K. E. Prenatal diagnosis of Duchenne muscular dystrophy by DNA analysis. J Med Genet. 1986 Dec;23(6):556–559. doi: 10.1136/jmg.23.6.556. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ott J. Estimation of the recombination fraction in human pedigrees: efficient computation of the likelihood for human linkage studies. Am J Hum Genet. 1974 Sep;26(5):588–597. [PMC free article] [PubMed] [Google Scholar]
  21. Read A. P., Kerzin-Storrar L., Mountford R. C., Elles R. G., Harris R. A register based system for gene tracking in Duchenne muscular dystrophy. J Med Genet. 1986 Dec;23(6):581–586. doi: 10.1136/jmg.23.6.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Read A. P., Mountford R. C., Forrest S. M., Kenwrick S. J., Davies K. E., Harris R. Patterns of exon deletions in Duchenne and Becker muscular dystrophy. Hum Genet. 1988 Oct;80(2):152–156. doi: 10.1007/BF00702859. [DOI] [PubMed] [Google Scholar]
  23. Sarfarazi M., Williams H. A computer programme for estimation of genetic risk in X linked disorders, combining pedigree and DNA probe data with other conditional information. J Med Genet. 1986 Feb;23(1):40–45. doi: 10.1136/jmg.23.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Williams H., Sarfarazi M., Brown C., Thomas N., Harper P. S. The use of flanking markers in prediction for Duchenne muscular dystrophy. Arch Dis Child. 1986 Mar;61(3):218–222. doi: 10.1136/adc.61.3.218. [DOI] [PMC free article] [PubMed] [Google Scholar]

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