Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Mutations in CEP57 cause mosaic variegated aneuploidy syndrome


Using exome sequencing and a variant prioritization strategy that focuses on loss-of-function variants, we identified biallelic, loss-of-function CEP57 mutations as a cause of constitutional mosaic aneuploidies. CEP57 is a centrosomal protein and is involved in nucleating and stabilizing microtubules. Our findings indicate that these and/or additional functions of CEP57 are crucial for maintaining correct chromosomal number during cell division.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: CEP57 structure, mutations and resulting aneuploidy.

Similar content being viewed by others

Accession codes


NCBI Reference Sequence


  1. Holland, A.J. et al. Nat. Rev. Mol. Cell Biol. 10, 478–487 (2009).

    Article  CAS  Google Scholar 

  2. Torres, E.M. et al. Genetics 179, 737–746 (2008).

    Article  CAS  Google Scholar 

  3. García-Castillo, H. et al. Am. J. Med. Genet. A. 146A, 1687–1695 (2008).

    Article  Google Scholar 

  4. Hanks, S. et al. Nat. Genet. 36, 1159–1161 (2004).

    Article  CAS  Google Scholar 

  5. Andersen, J.S. et al. Nature 426, 570–574 (2003).

    Article  CAS  Google Scholar 

  6. Momotani, K. et al. Biochem. J. 412, 265–273 (2008).

    Article  CAS  Google Scholar 

  7. Lane, A.H. et al. Am. J. Med. Genet. 110, 273–277 (2002).

    Article  Google Scholar 

  8. Meunier, S. et al. Traffic 10, 1765–1772 (2009).

    Article  CAS  Google Scholar 

  9. Musacchio, A. et al. Nat. Rev. Mol. Cell Biol. 8, 379–393 (2007).

    Article  CAS  Google Scholar 

  10. Suijkerbuijk, S.J. et al. Cancer Res. 70, 4891–4900 (2010).

    Article  CAS  Google Scholar 

  11. Forbes, S.A. et al. Nucleic Acids Res. 38, D652–D657 (2010).

    Article  CAS  Google Scholar 

  12. Ng, S.B. et al. Hum. Mol. Genet. 19, R119–R124 (2010).

    Article  CAS  Google Scholar 

  13. Ng, S.B. et al. Nat. Genet. 42, 790–793 (2010).

    Article  CAS  Google Scholar 

Download references


We are very grateful to all the families that participated in this study and to A. Zachariou, M. Warren-Perry, R. Linger, D. Dudakia and J. Bull for assistance in their recruitment. We thank D. Leongamornlert for assistance with exome sequencing, A. Renwick, S. Seal, G. Bowden, D. Hughes and C. Turnbull for assistance in Solexa optimization and validation experiments and B. Ebbs for DNA extraction and for running the ABI sequencer. We thank K. Tatton-Brown for assistance with clinical review of cases, A.I. Vasquez and J. Swansbury for the karyotyping and A. Strydom for secretarial assistance with the manuscript. K.S. is supported by the Michael and Betty Kadoorie Cancer Genetics Research Programme. We acknowledge NHS funding to the National Institute for Health Research Biomedical Research Centre. This work was supported by Cancer Research UK (grants C8620_A9024 and C8620_A8857) and the Institute of Cancer Research (UK).

Author information

Authors and Affiliations



S.H., J.D. and A.M. performed exome sequencing. K.S., E.R., A.E. and N.R. performed data management and analysis. S.H. and J.D. performed CEP57 mutation and dosage analysis. P.B.-N., A.H.L., N.S., P.C., D.C., J.C.-S., D.R.F., D.G., S.J., K.A.-H., M.A.M., J.T., P.D.T. and M.W. provided clinical material. N.R. wrote the manuscript with substantial input from K.S., S.H., E.R. and J.D. N.R. designed and oversaw all aspects of the study.

Corresponding author

Correspondence to Nazneen Rahman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Tables 1–5 and Supplementary Figures 1–4. (PDF 3220 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Snape, K., Hanks, S., Ruark, E. et al. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet 43, 527–529 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing