Skip to main content
SpringerLink
Log in

Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats

  • Letter
  • Published:

From Nature

View current issue Submit your manuscript

Abstract

LISSENCEPHALY (agyria-pachygyria) is a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration1,2. Identification of the gene(s) involved in this disorder would facilitate molecular dissection of normal events in brain development3. Type 1 lissencephaly occurs either as an isolated abnormality or in association with dysmorphic facial appearance in patients with Miller–Dieker syndrome4,5. About 15% of patients with isolated lissencephaly and more than 90% of patients with Miller–Dieker syndrome have microdeletions in a critical 350-kilobase region in chromosome 17p13.3 (ref. 6). These deletions are hemizygous, so haplo-insufficiency for a gene in this interval is implicated. Here we report the cloning of a gene (LIS-1, lissencephaly-1) in 17p13.3 that is deleted in Miller–Dieker patients. Non-overlapping deletions involving either the 5' or 3' end of the gene were found in two patients, identifying LIS-l as the disease gene. The deduced amino-acid sequence shows significant homology to β-subunits of heterotrimeric G proteins, suggesting that it could possibly be involved in a signal transduction pathway crucial for cerebral development.

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

Similar content being viewed by others

References

  1. Aicardi, J. Int. Pediatr. 4, 118–126 (1989).

    Google Scholar 

  2. Dobyns, W. B. Neurol. Clin. 7, 89–105 (1989).

    Article  CAS  Google Scholar 

  3. Barth, P. G. Can. J. Neurol. Sci. 14, 1–16 (1987).

    Article  CAS  Google Scholar 

  4. Miller, J. Q. Neurology 13, 841–850 (1963).

    Article  CAS  Google Scholar 

  5. Dieker, H. et. al. The Lissencephaty Syndrome. The Clinical Delineation of Birth Defects II: Malformation Syndromes 1–64 (National Foundation March of Dimes, New York, 1969).

    Google Scholar 

  6. Ledbetter, S. A., Kuwano, A., Dobyns, W. B. & Ledbetter, D. H. Am. J. hum. Genet. 50, 182–189 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Duronio, R. J., Gordon, J. I. & Boguski, M. S. Proteins 13, 41–56 (1992).

    Article  CAS  Google Scholar 

  8. Lee, C. C. et al. Science 239, 1288–1291 (1988).

    Article  ADS  CAS  Google Scholar 

  9. Guillemot, F., Billault, A. & Auffray, C. Proc. natn. Acad. Sci. U.S.A. 86, 4594–4598 (1989).

    Article  ADS  CAS  Google Scholar 

  10. Guzzetta, V. et al. Genomics 13, 551–559 (1992).

    Article  CAS  Google Scholar 

  11. Dobyns, W. B., Curry, C. J. R., Hoyme, H. E., Turlington, L. & Ledbetter, D. H. Am. J. hum. Genet. 48, 584–594 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Ledbetter, D. H. et al. Proc. natn. Acad. Sci. U.S.A. 86, 5136–5140 (1989).

    Article  ADS  CAS  Google Scholar 

  13. Leberer, E., Dignard, D., Hougan, L., Thomas, D. Y. & Whiteway, M. EMBO J. 11, 4805–4813 (1992).

    Article  CAS  Google Scholar 

  14. Birnbaumer, L. Cell 71, 1069–1072 (1992).

    Article  CAS  Google Scholar 

  15. Simon, M. I., Strathmann, M. P. & Gautam, N. Science 252, 802–808 (1991).

    Article  ADS  CAS  Google Scholar 

  16. Gilman, A. G. A. Rev. Biochem. 56, 615–649 (1987).

    Article  CAS  Google Scholar 

  17. Kleuss, C., Scherubl, H., Hescheler, J., Schultz, G. & Wittig, B. Science 259, 832–834 (1993).

    Article  ADS  CAS  Google Scholar 

  18. Iniguez-Lluhi, J. A., Simon, M. I., Robishaw, J. D. & Gilman, A. G. J. biol. Chem. 267, 23409–23417 (1992).

    CAS  Google Scholar 

  19. Bourne, H. R. & Nicholl, R. Cell 72, 65–76 (1993).

    Article  Google Scholar 

  20. Igarashi, M., Strittematter, S. M., Vartanian, T. & Fishman, M. C. Science 259, 77–79 (1993).

    Article  ADS  CAS  Google Scholar 

  21. Nishimoto, I. et al. Nature 362, 75–79 (1993).

    Article  ADS  CAS  Google Scholar 

  22. Keleher, C. A., Redd, M. J., Schultz, J., Carlson, M. & Johnson, A. D. Cell 68, 709–719 (1992).

    Article  CAS  Google Scholar 

  23. Orikin, S. H. & Nathan, D. G. New Engl. J. Med. 295, 710–714 (1976).

    Article  Google Scholar 

  24. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. J. molec. Biol. 215, 403–410 (1990).

    Article  CAS  Google Scholar 

  25. Bilofsky, H. S. & Burks, C. Nucleic Acids Res. 16, 1861–1864 (1988).

    Article  CAS  Google Scholar 

  26. van Tuinen, P., Rich, D. C., Summers, K. M. & Ledbetter, D. H. Genomics 1, 374–381 (1987).

    Article  CAS  Google Scholar 

  27. Sambrook, S., Fritisch, E. I. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, New York, 1989).

    Google Scholar 

  28. Kuwano, A., Ledbetter, S. A., Dobyns, W. B., Emanuel, B. S. & Ledbetter, D. H. Am. J. hum. Genet. 49, 707–714 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Kuwano, A. et al. Hum. molec. Genet. 1, 417–425 (1992).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas, 77030, USA

    Orly Reiner, Romeo Carrozzo, Ying Shen, Manfred Wehnert, Fabrizia Faustinella, C. Thomas Caskey & David H. Ledbetter

  2. Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, 77030, USA

    C. Thomas Caskey

  3. Division of Pediatric Neurology, Departments of Neurology and Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, 55455, USA

    William B. Dobyns

Authors
  1. Orly Reiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Romeo Carrozzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manfred Wehnert
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabrizia Faustinella
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William B. Dobyns
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Thomas Caskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. David H. Ledbetter
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reiner, O., Carrozzo, R., Shen, Y. et al. Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats. Nature 364, 717–721 (1993). https://doi.org/10.1038/364717a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/364717a0

  • Springer Nature Limited

This article is cited by

Search

Navigation