Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B

S Hanks, K Coleman, S Reid, A Plaja, H Firth… - Nature …, 2004 - nature.com
S Hanks, K Coleman, S Reid, A Plaja, H Firth, D FitzPatrick, A Kidd, K Méhes, R Nash…
Nature genetics, 2004nature.com
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 …
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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