Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B

Nat Genet. 2004 Nov;36(11):1159-61. doi: 10.1038/ng1449. Epub 2004 Oct 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Alleles
  • Aneuploidy*
  • Cell Cycle Proteins
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Sequence Data
  • Mosaicism
  • Mutation*
  • Neoplasms / genetics*
  • Protein Kinases / genetics*
  • Protein-Serine-Threonine Kinases
  • Spindle Apparatus

Substances

  • Cell Cycle Proteins
  • Protein Kinases
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/AF046079
  • OMIM/257300
  • SWISSPROT/Q800D4
  • SWISSPROT/Q8JGT8
  • SWISSPROT/Q9Z1S0