Advertisement

European Journal of Pediatrics

, Volume 150, Issue 4, pp 256–258 | Cite as

Prenatal deletion detection in a sporadic case of Duchenne muscular dystrophy without genotype information from the affected individual

  • F. Peinemann
  • M. Wagner
  • U. Franke
  • M. Kulle
  • J. Reiss
Medical Genetics

Abstract

We describe the application of deletion screening by amplification of deletion-prone exons via polymerase chain reaction (PCR) in a family with a sporadic case of Duchenne muscular dystrophy (DMD). No DNA was available from the affected patient who died 12 years beforehand at the age of 18 years. Material obtained prenatally from two male fetuses exhibited an identical deletion. These findings effectivly transformed a sporadic case into a familial case and a numerical carrier risk was substituted by obligate carrier status. Additionally an indirect genotype analysis was replaced by the possibility of direct DNA analysis. Genetic counselling, formerly based upon incomplete data, can now be aided by precise risk assessment.

Key words

Duchenne muscular dystrophy Deletion screening Prenatal diagnosis Polymerase chain reaction 

Abbreviations

CK

creatine kinase

DMD

Duchenne muscular dystrophy

PCR

polymerase chain reaction

RFLP

restriction fragment length polymorphism

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bakker E, Hofker MH, Goor N, Mandel JL, Wrogemann K, Davies KE, Kunkel LM, Willard HF, Fenton WA, Sandkuyl L, Majoor-Krakauer D, Van Essen AJ, Jahoda MGH, Sachs E, Van Ommen GJB, Pearson PL (1985) Prenatal diagnosis and carrier detection of Duchenne muscular dystrophy with closely linked RFLPs. Lancet I:655–658Google Scholar
  2. 2.
    Bakker E, Van Broeckhoven C, Bonten EJ, Vooren MJ van de, Veenema H, Van Hul W, Van Ommen GJB, Vandenberghe, Pearson PL (1987) Germline mosaicism and Duchenne muscular dystrophy mutations. Nature 329:554–556PubMedGoogle Scholar
  3. 3.
    Bundey S, Crawley JM, Edwards JH, Westhead RA (1979) Serum creatine kinase levels in pubertal, mature, pregnant, and postmenopausal women. J Med Genet 16:117–121PubMedGoogle Scholar
  4. 4.
    Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT (1988) Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 16 (23):11141–11156PubMedGoogle Scholar
  5. 5.
    Darras BT, Blattner P, Harper JF, Spiro AJ, Alter S, Francke U (1988) Intragenic deletions in 21 Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) families studied with the dystrophin cDNA: location of breakpoints on HindIII and BgIII exon-containing fragment maps, meiotic and mitotic origin of the mutations. Am J Hum Genet 43:620–629PubMedGoogle Scholar
  6. 6.
    Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13PubMedGoogle Scholar
  7. 7.
    Grimm T, Müller B, Dreier M, Kind E, Bettecken T, Meng G, Müller CR (1989) Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene. Am J Hum Genet 45:368–372PubMedGoogle Scholar
  8. 8.
    Haldane JBS (1935) The rate of spontaneous mutations of a human gene. J Genet 31:317–326Google Scholar
  9. 9.
    Hentemann M, Reiss J, Wagner M, Cooper DN (1990) Rapid detection of deletions in the Duchenne muscular dystrophy gene by PCR amplification of deletion-prone exon sequences. Hum Genet 84:228–232PubMedGoogle Scholar
  10. 10.
    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 organization of the DMD gene in normal and affected individuals. Cell 50:509–517PubMedGoogle Scholar
  11. 11.
    Koenig M, Monaco AP, Kunkel LM (1988) The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53:219–228PubMedGoogle Scholar
  12. 12.
    Kogan SC, Doherty M, Gitschier J (1987) An improved method for prenatal diagnosis of genetic diseases by analysis of amplified DNA sequences: application to hemophilia A. N Engl J Med 317:985–990PubMedGoogle Scholar
  13. 13.
    Lathrop GM, Lalouel JM (1984) Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet 36:460–465PubMedGoogle Scholar
  14. 14.
    Mandel JL (1989) The gene and its product. Nature 339:584–586PubMedGoogle Scholar
  15. 15.
    Nicholson GA, Gardner-Medwin D, Pennington RJT, Walton JN (1979) Carrier detection in Duchenne muscular dystrophy: assessment of the effect of age on detection-rate with serum-creatine-kinase-activity. Lancet I:692–694Google Scholar
  16. 16.
    Roberts RG, Cole CG, Hart KA, Bobrow M, Bentley DR (1989) Rapid carrier and prenatal diagnosis of Duchenne and Becker muscular dystrophy. Nucleic Acids Res 17 (2):811PubMedGoogle Scholar
  17. 17.
    Russo A, Barbujani G, Mostacciuolo ML, Herrmann FH, Spiegler AWJ, Galluzzi G, Danieli GA (1987) Sporadic cases in Duchenne muscular dystrophy. Hum Genet 76:230–235PubMedGoogle Scholar
  18. 18.
    Worton RG, Thompson MW (1988) Genetics of Duchenne muscular dystrophy. Annu Rev Genet 22:601–629PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • F. Peinemann
    • 1
  • M. Wagner
    • 1
  • U. Franke
    • 1
  • M. Kulle
    • 1
  • J. Reiss
    • 1
  1. 1.Institut für Humangenetik der Universität GöttingenGöttingenFederal Republic of Germany

Personalised recommendations