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Mutations in CEP57 cause mosaic variegated aneuploidy syndrome

Abstract

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.

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Figure 1: CEP57 structure, mutations and resulting aneuploidy.

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NCBI Reference Sequence

References

  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 

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Acknowledgements

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).

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Authors

Contributions

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.

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Correspondence to Nazneen Rahman.

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The authors declare no competing financial interests.

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

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Snape, K., Hanks, S., Ruark, E. et al. Mutations in CEP57 cause mosaic variegated aneuploidy syndrome. Nat Genet 43, 527–529 (2011). https://doi.org/10.1038/ng.822

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