Skip to main content
SpringerLink
Log in

Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis

  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose: Preimplantation genetic diagnosis (PGD) has been performed for deletion and point mutation type of Duchenne muscular dystrophy (DMD). Our aim was to develop a PGD technique, not yet established, to directly detect duplication mutation instead of substitute diagnosis similar to gender determination.

Methods: Our method is based on comparative quantification using conventional duplex PCR, real-time PCR and gender determination. We evaluated this method in single lymphocytes from a duplication type of DMD patient and a normal male.

Results: There was a significant difference in the mean values of the ratios (the mutation locus/a normal reference): mean value ± SE was 1.84 ± 0.15 in the duplication patient, and 1.00 ± 0.09 in the normal male (p < 0.001).

Conclusion: It is suggested that our comparative quantification method could be a new option in PGD for carriers with duplication mutation who wish to have an unaffected son.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Roberts RG. Dystrophin, its gene, and the dystrophinopathies. Adv Genet 1995;33:177–231.

    PubMed  CAS  Google Scholar 

  2. Matsuo M. Duchenne and Becker muscular dystrophy: from gene diagnosis to molecular therapy. IUBMB Life 2002;53:147–52.

    Article  PubMed  CAS  Google Scholar 

  3. Kapsa R, Kornberg AJ, Byrne E. Novel therapies for Duchenne muscular dystrophy. Lancet Neurol 2003;2(5):299–310.

    Article  PubMed  CAS  Google Scholar 

  4. Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987;51:917–28.

    Article  Google Scholar 

  5. den Dunnen JT, Grootscholten PM, Bakker E, Blonden LAJ, Ginjaar HB, Wapenaar MC. 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;45:835–47.

    PubMed  CAS  Google Scholar 

  6. Tennyson CN, Klamut HJ, Worton RG. The human dystrophin gene requires 16 h to be transcribed and its contranscriptionally spliced. Nature Genet 1995;9:184–90.

    Article  PubMed  CAS  Google Scholar 

  7. Braude P, Pickering S, Flinter F, Mackie Ogilvie C. Preimplantation genetic diagnosis. Nat Rev Genet 2002;3:941–55.

    Article  CAS  Google Scholar 

  8. Saiki RK, et al. Enzymatic amplification of β-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science 1985;230:1350–4.

    Article  PubMed  CAS  Google Scholar 

  9. Handyside AH, Kontogianni EH, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature 1990;344:768–70.

    Article  PubMed  CAS  Google Scholar 

  10. Handyside AH, Lesko JG, Tarin JJ, Winston RM, Hughes MR. Birth of a normal girl after in vitro fertilization and preimplantation diagnostic testing for cystic fibrosis. N Engl L Med 1992;327:905–9.

    Article  CAS  Google Scholar 

  11. Pierre Ray F, Vekemans M, Munnich A. Single cell multiplex PCR amplification of five dystrophin gene exons combined with gender determination. Mol Hum Reprod 2001;7:489–94.

    Article  Google Scholar 

  12. Liu J, Lissens W, Van Broeckhoven C, et al. Normal pregnancy after preimplantation DNA diagnosis of a dystrophin gene deletion. Prenat Diagn 1995;15:351–8.

    Article  PubMed  CAS  Google Scholar 

  13. Hussey ND, Donggui H, Froiland DA, et al. Analysis of five Duchenne muscular dystrophy exons and gender determination using conventional duplex polymerase chain reaction on single cells. Mol Hum Reprod 1999;5:1089–94.

    Article  PubMed  CAS  Google Scholar 

  14. Ray PF, Vekemans M, Munnich A. Single cell multiplex PCR amplification of five dystrophin gene exons conbined with gender determination. Mol Hum Reprod 2001;7:489–94.

    Article  PubMed  CAS  Google Scholar 

  15. Girardet A, Hamamah S, Dechaud H, et al. Specific detection of deleted and non-deleted dystrophin exons together with gender assignment in preimplantation genetic diagnosis of Duchenne muscular dystrophy. Mol Hum Reprod 2003;9:421–27.

    Article  PubMed  CAS  Google Scholar 

  16. Roberts RG, Bobrow M, Bentley DR. Point mutations in the dystrophin gene. PNAS 1992;89:2331–5.

    Article  PubMed  CAS  Google Scholar 

  17. Hu XY, Ray PN, Murphy EG, Tompson NW, Worton RG. Duplicational mutation at the Duchenne muscular dystrophy locus: its frequency, distribution, origin, and phenotype genotype correlation. Am J Hum Genet 1990;46:682–95.

    PubMed  CAS  Google Scholar 

  18. Carvalho F, Sousa M, Fernandes S. Preimplantation genetic diagnosis for familial amyloidotic polyneuropathy (FAP). Prenat Diagn 2001;21(12):1093–9.

    Article  PubMed  CAS  Google Scholar 

  19. Hussey ND, Davis T, Hall JR, et al. Preimplantation genetic diagnosis for β-thalassaemia using sequencing of single cell PCR products to detect mutations and polymorphic loci. Mol Hum Repro 2002;8:1136–43.

    Article  CAS  Google Scholar 

  20. Blair IP, Kennerson ML, Nicholson GA. Detection of Charcot-Marie-Tooth type 1A duplication by the polymerase chain reaction. Clin Chem 1995;41:1105–8.

    PubMed  CAS  Google Scholar 

  21. Navon R, Timmerman V, Lofgren A, et al. Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A (CMT1A) using molecular genetic techniques. Prenat Diagn 1995;15:633–40.

    Article  PubMed  CAS  Google Scholar 

  22. De Vos A, Sermon K, Van de Velde H. Pregnancy after preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A. Mol Hum Reprod 1998;4(10):978–84.

    Article  PubMed  CAS  Google Scholar 

  23. Tsuchiya S, Sueoka K, Matsuda N, et al. The “Spanning protocol”: A new DNA extraction method for efficient single-cell diagnosis. J Assist Reprod Genet 2005;22:407–14.

    Article  PubMed  Google Scholar 

  24. Chamberlain JS, Gibbs RA, Rainier JE, Vaskey CT. A guide to Methods and Applications. In: Innis M, Gelfand DH, Sninsky JJ, White TJ, editors. PCR protocols. Academic Press; 1990. p. 272–81.

    Google Scholar 

  25. Beggs AH, Koenig M, Boyce FM, Kunkel LM. Detection of 98% of DMD/BMD gene deletions by polymerase chain reaction. Hum Genet 1990;86:45–8.

    Article  PubMed  CAS  Google Scholar 

  26. Cui KH, Hann EA, Wang LJ, et al. Sex determination of preimplantation embryos by human-determination-gene amplification. Lancet 1994;343:79–82.

    Article  PubMed  CAS  Google Scholar 

  27. Livak KJ. Comparative Ct method. In: ABI Prism 7700 Sequence Detection System. User Bulletin no. 2. PE Applied Biosystems; 1997.

  28. Armour JA, Barton DE, Cockburn DJ, Taylor GR. The detection of large deletions or duplications in genomic DNA. Hum Mutat 2002;20:325–37.

    Article  PubMed  CAS  Google Scholar 

  29. Joncourt F, Neuhaus B, Jostarndt-Foegen K, Kleinle S, Steiner B, Gallati S. Rapid identification of female carriers of DMD/BMD by quantitative real-time PCR. Hum Mutat 2004;23(4):385–91.

    Article  PubMed  CAS  Google Scholar 

  30. Nina K Aarskog, Christian A Vedeler. Real-time quantitative polymerase chain reaction-A new method that detects both the peripheral myelin protein 22 duplication in Charcot-Marie-Tooth type 1A disease and the peripheral myelin protein 22 detection in hereditary neuropathy with liability to pressure palsies. Hum Genet 2000;107:494–8.

    Article  Google Scholar 

  31. Fiorentino F, Biricik A, Nuccitelli A, et al. Strategies and clinical outcome of 250 cycles of Preimplantation Genetic Diagnosis for single gene disorders. Hum Reprod 2005;25:1–15.

    Google Scholar 

Download references

Acknowledgments

We wish to thank Dr. Tadayuki Ishihara, and the late Dr. Jun Kawamura affiliated with the National Higashisaitama Hospital, for supplying blood of DMD patients who received treatment for their disease.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo #160-8582, Japan

    Akira Nakabayashi, Kou Sueoka, Hiroto Tajima, Kenji Sato, Yoshiaki Sakamoto & Yasunori Yoshimura

  2. Department of Microbiology and immunology, Keio University School of Medicine, 35 Shinanomachi Shinjuku-ku, Tokyo #160-8582, Japan

    Shingo Katou

Authors
  1. Akira Nakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kou Sueoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroto Tajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kenji Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yoshiaki Sakamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shingo Katou
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yasunori Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akira Nakabayashi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakabayashi, A., Sueoka, K., Tajima, H. et al. Well-devised quantification analysis for duplication mutation of Duchenne muscular dystrophy aimed at preimplantation genetic diagnosis. J Assist Reprod Genet 24, 233–240 (2007). https://doi.org/10.1007/s10815-007-9111-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-007-9111-3

Keywords

Search

Navigation