Abstract
Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses. In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, we identified truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint. These data are the first to relate germline mutations in a spindle checkpoint gene with a human disorder and strongly support a causal link between aneuploidy and cancer development.
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Acknowledgements
We thank all the families that gave informed consent to take part in this research; the many clinicians that were involved in their diagnosis and management, including D. Bain, H. Cox, A. Green, A. McEwen, T. Vendrell, P. Ellis and R. Murray; M. Stratton and A. Futreal for advice on the manuscript; and K. Tatton-Brown and T. Min for help in preparation of the figure. A.I. is supported by Tenovus the Cancer Charity. This research was supported and approved by the Institute of Cancer Research (UK).
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Hanks, S., Coleman, K., Reid, S. et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet 36, 1159–1161 (2004). https://doi.org/10.1038/ng1449
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DOI: https://doi.org/10.1038/ng1449
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