Subjects

  • A Corrigendum to this article was published on 01 May 2005

Abstract

Autosomal recessive primary microcephaly is a potential model in which to research genes involved in human brain growth. We show that two forms of the disorder result from homozygous mutations in the genes CDK5RAP2 and CENPJ. We found neuroepithelial expression of the genes during prenatal neurogenesis and protein localization to the spindle poles of mitotic cells, suggesting that a centrosomal mechanism controls neuron number in the developing mammalian brain.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

References

  1. 1.

    & Curr. Opin. Neurol. 14, 151–156 (2001).

  2. 2.

    et al. J. Med. Genet. 39, 718–721 (2002).

  3. 3.

    et al. Nat. Genet 32, 316–320 (2002).

  4. 4.

    Curr. Opin. Neurobiol. 14, 112–117 (2004).

  5. 5.

    et al. Am. J. Hum. Genet. 73, 1170–1177 (2003).

  6. 6.

    et al. Am. J. Hum. Genet. 71, 136–142 (2002).

  7. 7.

    et al. Am. J. Hum. Genet. 75, 261–266 (2004).

  8. 8.

    , & J. Biol. Chem. 279, 34091–34094 (2004).

  9. 9.

    , & J. Cell. Biol. 153, 637–648 (2001).

  10. 10.

    et al. Am. J. Hum. Genet. 66, 724–727 (2000).

  11. 11.

    et al. J. Med. Genet. 40, 540–542 (2003).

  12. 12.

    et al. Nature 426, 570–574 (2003).

  13. 13.

    , , , & Mol. Biol. Cell 15, 2697–2706 (2004).

  14. 14.

    et al. J. Biol. Chem. 275, 21041–21047 (2000).

  15. 15.

    , , , & Clin. Genet. 66, 341–348 (2004).

Download references

Acknowledgements

We thank the families who participated with this study. J.B., E.R., K.S., S.S., J.H.,H.J. and C.G.W. are supported by the Wellcome Trust. D.J.H. is supported by the Medical Research Council. S.L. is funded by US National Institutes of Health. E.E.M. is supported by Cancer Research UK. C.A.W. is supported by The National Institute of Neurological Disorders and Stroke and The March of Dimes.

Author information

Author notes

    • Jacquelyn Bond
    •  & Emma Roberts

    These authors contributed equally to this work.

Affiliations

  1. Molecular Medicine Unit, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

    • Jacquelyn Bond
    • , Emma Roberts
    • , Kelly Springell
    • , Sheila Scott
    • , Julie Higgins
    •  & Daniel J Hampshire
  2. Division of Neurogenetics, Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, 4 Blackfan Circle, Boston, Massachusetts 02115, USA.

    • Sophia Lizarraga
    •  & Christopher A Walsh
  3. Cancer Research UK Centre at Leeds, Division of Cancer Medicine Research, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

    • Ewan E Morrison
  4. Instituto Materno-Infantil de Pernambuco, Recife-PE, Brazil.

    • Gabriella F Leal
    •  & Elias O Silva
  5. Departamento de Genética, Universidade Federal de Pernambuco, Recife-PE, Brazil.

    • Suzana M R Costa
  6. Department of Medical Genetics, CIMR, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge CB2 2BP, UK.

    • Diana Baralle
    • , Michela Raponi
    •  & C Geoffrey Woods
  7. Department of Clinical Genetics, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.

    • Gulshan Karbani
    •  & Christopher Bennett
  8. Department of Obstetrics and Gynaecology, Lady Wellington Hospital, Lahore, Pakistan.

    • Yasmin Rashid
    •  & Hussain Jafri
  9. Department of Paediatrics, St. Luke's Hospital, Bradford, UK.

    • Peter Corry

Authors

  1. Search for Jacquelyn Bond in:

  2. Search for Emma Roberts in:

  3. Search for Kelly Springell in:

  4. Search for Sophia Lizarraga in:

  5. Search for Sheila Scott in:

  6. Search for Julie Higgins in:

  7. Search for Daniel J Hampshire in:

  8. Search for Ewan E Morrison in:

  9. Search for Gabriella F Leal in:

  10. Search for Elias O Silva in:

  11. Search for Suzana M R Costa in:

  12. Search for Diana Baralle in:

  13. Search for Michela Raponi in:

  14. Search for Gulshan Karbani in:

  15. Search for Yasmin Rashid in:

  16. Search for Hussain Jafri in:

  17. Search for Christopher Bennett in:

  18. Search for Peter Corry in:

  19. Search for Christopher A Walsh in:

  20. Search for C Geoffrey Woods in:

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to C Geoffrey Woods.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    Genotyping of the MCPH3 region.

  2. 2.

    Supplementary Fig. 2

    Genotyping of the MCPH6 region.

  3. 3.

    Supplementary Fig. 3

    Overview of the positional cloning of the MCPH3 locus and identification of mutations in the CDK5RAP2 gene.

  4. 4.

    Supplementary Fig. 4

    Overview of the positional cloning of the MCPH6 locus and the identification of mutations in the CENPJ gene.

  5. 5.

    Supplementary Fig. 5

    CDK5RAP2 IVS26-15A>G minigene splicing assay confirming the mutation creates a superior splice acceptor site.

  6. 6.

    Supplementary Fig. 6

    Alignment comparison of intron 26-Exon 27 CDK5RAP2 and a section of the Tcp10 domain of CENPJ, indicating MCPH mutations and their outcome.

  7. 7.

    Supplementary Fig. 7

    Mouse embryonic brain expression profiles of Cdk5rap2 and Cenpj.

  8. 8.

    Supplementary Table 1

    MCPH3 and MCPH6 genotyping information.

  9. 9.

    Supplementary Methods

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/ng1539

Further reading