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variegated mosaic aneuploidy syndrome

MIM.257300

Tuesday 25 November 2003

Definition: Mosaic variegated aneuploidy is a rare recessive condition characterized by growth retardation, microcephaly, childhood cancer and constitutional mosaicism for chromosomal gains and losses.The mosaic variegated aneuploidy syndrome can be caused by mutation in the BUB1B gene (MIM.602860), which encodes a key protein in the mitotic spindle checkpoint.

Synopsis

- constitutional aneuploidies
- premature centromere division
- growth deficiency
- mild physical anomalies
- mental retardation
- cataracts (18548531)
- cerebral malformations

- tumor predisposition

Etiology

- germline mutations in BUB1B (MIM.602860),

  • BUB1B gene encodes a key protein in the mitotic spindle checkpoint.

In five families with mosaic variegated aneuploidy, including two with embryonal rhabdomyosarcoma, truncating and missense mutations of BUB1B, which encodes BUBR1, a key protein in the mitotic spindle checkpoint, have been identified. (15475955)

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. (15475955).

See also

- premature chromatid separation (PCS) (MIM.176430)

  • PCS can be caused by heterozygous mutation in the BUB1B gene.
  • PCS is inherited as an autosomal dominant trait without phenotypic consequences.

References

- Hanks S, Coleman K, Summersgill B, Messahel B, Williamson D, Pritchard-Jones K, Strefford J, Swansbury J, Plaja A, Shipley J, Rahman N. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer Lett. 2006 Aug 8;239(2):234-8. PMID: 16182441

- 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. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat Genet. 2004 Nov;36(11):1159-61. PMID: 15475955

- Furukawa T, Azakami S, Kurosawa H, Ono Y, Ueda Y, Konno Y. Cystic partially differentiated nephroblastoma, embryonal rhabdomyosarcoma, and multiple congenital anomalies associated with variegated mosaic aneuploidy and premature centromere division: a case report. J Pediatr Hematol Oncol. 2003 Nov;25(11):896-9. PMID: 14608201