Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B

• Published in: Nature genetics Vol. 36; no. 11; pp. 1159 - 1161
• Main Authors: Méhes, Károly, Shannon, Nora, FitzPatrick, David, Reid, Sarah, Douglas, Jenny, Firth, Helen, Plaja, Alberto, Robin, Nathanial, Irrthum, Alexandre, Nash, Richard, Tolmie, John, Kidd, Alexa, Swansbury, John, Coleman, Kim, Hanks, Sandra, Rahman, Nazneen
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-11-2004
• Subjects: Abnormalities, Multiple - genetics; Alleles; Aneuploidy; Biological and medical sciences; Cancer; Cell Cycle Proteins; Chromosome aberrations; Complications and side effects; Diagnosis; Fundamental and applied biological sciences. Psychology; Gene mutations; Genetic aspects; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Humans; Identification and classification; Malformations of the nervous system; Medical genetics; Medical sciences; Molecular Sequence Data; Mosaicism; Mutation; Neoplasms - genetics; Neurology; Protein Kinases - genetics; Protein-Serine-Threonine Kinases; Risk factors; Spindle Apparatus; United Kingdom; Chromosomal aberration; Human; Nervous system diseases; Embryonal rhabdomyosarcoma; Aneuploidy; Malignant tumor; Microcephaly; Congenital disease; Mitotic spindle; Protein; Growth retardation; Cerebral disorder; Striated muscle disease; Missense mutation; Gene; Malformation; Germ line; Central nervous system disease; Cell cycle; Predisposition; Mosaicism; Control point
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1449

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.