Authors: Hanks S; Coleman K; Reid S; Plaja A; Firth H; Fitzpatrick D; Kidd A; Méhes K; Nash R; Robin N; Shannon N; Tolmie J; Swansbury J; Irrthum A; Douglas J; Rahman N
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.Keywords: Abnormalities, Multiple/*genetics; Alleles; *Aneuploidy; Cell Cycle Proteins; Genetic Predisposition to Disease; Humans; Mitotic Spindle Apparatus; Molecular Sequence Data; Mosaicism; *Mutation; Neoplasms/*genetics; Protein Kinases/*genetics; Protein-Serine-Threonine Kinases
Journal: Nature genetics
Date: Oct. 12, 2004
Select reference article to upload
Hanks S, Coleman K, Reid S, Plaja A, Firth H, Fitzpatrick D, Kidd A, Méhes K, Nash R, Robin N, Shannon N, Tolmie J, Swansbury J, Irrthum A, Douglas J, Rahman N (2004) Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nature genetics 36: 1159-61.