Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.
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.
Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, UK.
Sandra
S
Hanks
Kim
K
Coleman
Sarah
S
Reid
Alberto
A
Plaja
Helen
H
Firth
David
D
Fitzpatrick
Alexa
A
Kidd
Károly
K
Méhes
Richard
R
Nash
Nathanial
N
Robin
Nora
N
Shannon
John
J
Tolmie
John
J
Swansbury
Alexandre
A
Irrthum
Jenny
J
Douglas
Nazneen
N
Rahman
D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D000782:Aneuploidy; D018797:Cell Cycle Proteins; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus
D018797:Cell Cycle Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases