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A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size

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.

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Figure 1: Clinical features of MCPH and the identification of pathogenic mutations in CDK5RAP2 (at locus MCPH3) and CENPJ (at locus MCPH6).
Figure 2: Expression profiles of CDK5RAP2 and CENPJ.

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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.

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Correspondence to C Geoffrey Woods.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Genotyping of the MCPH3 region. (PDF 18 kb)

Supplementary Fig. 2

Genotyping of the MCPH6 region. (PDF 24 kb)

Supplementary Fig. 3

Overview of the positional cloning of the MCPH3 locus and identification of mutations in the CDK5RAP2 gene. (PDF 23 kb)

Supplementary Fig. 4

Overview of the positional cloning of the MCPH6 locus and the identification of mutations in the CENPJ gene. (PDF 22 kb)

Supplementary Fig. 5

CDK5RAP2 IVS26-15A>G minigene splicing assay confirming the mutation creates a superior splice acceptor site. (PDF 33 kb)

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. (PDF 17 kb)

Supplementary Fig. 7

Mouse embryonic brain expression profiles of Cdk5rap2 and Cenpj. (PDF 10981 kb)

Supplementary Table 1

MCPH3 and MCPH6 genotyping information. (PDF 10 kb)

Supplementary Methods (PDF 24 kb)

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Bond, J., Roberts, E., Springell, K. et al. A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 37, 353–355 (2005). https://doi.org/10.1038/ng1539

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