Letter | Published:

Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis

Abstract

THE fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis1. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women2. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site3–6. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination1,7,8 or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells9,10. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Nussbaum, R. L. & Ledbetter, D. H. A. Rev. Genet. 20, 109–145 (1986).

  2. 2

    Sherman, S. L. Jacobs, P. A. Morton, N. E., Froster-Iskenius, U. & Howard-Peebles, P. N. Hum. Genet. 69, 289–299 (1985).

  3. 3

    Oberlé, I. et al. Proc. natn. Acad Sci. U.S.A. 83, 1016–1020 (1986).

  4. 4

    Suthers, G. K. et al. Science 246, 1298–1300 (1989).

  5. 5

    Suthers, G. K. et al. Am. J. hum. Genet. 47, 187–195 (1990).

  6. 6

    Rousseau, F. et al. Am. J. hum. Genet. 48, 108–116 (1991).

  7. 7

    Pembrey, M. E., Winter, R. & Davies, K. Am. J. med. Genet. 21, 709–717 (1985).

  8. 8

    Ledbetter, D. H., Ledbetter, S. A. & Nussbaum, R. L. Nature 324, 161–163 (1986).

  9. 9

    Laird, C. D. Genetics 117, 587–599 (1987).

  10. 10

    Laird, C. D., Lamb, M. M. & Thorne, J. L. Am. J. hum. Genet. 46, 696–719 (1990).

  11. 11

    Warren, S. T. et al. Proc. natn. Acad Sci. U.S.A. 87, 3856–3860 (1989).

  12. 12

    Suthers, G. K. et al. Am. J. hum. Genet. (in the press).

  13. 13

    Bird, A. P. Trends Genet. 3, 342–347 (1987).

  14. 14

    Southern, E. M., Anand, R., Brown, W. R. A. & Fletcher, D. S. Nucleic Acids Res. 15, 5925–5943 (1987).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.