Mosaic variegated aneuploidy in development, ageing and cancer

Abstract

Mosaic variegated aneuploidy (MVA) is a rare condition in which abnormal chromosome counts (that is, aneuploidies), affecting different chromosomes in each cell (making it variegated) are found only in a certain number of cells (making it mosaic). MVA is characterized by various developmental defects and, despite its rarity, presents a unique clinical scenario to understand the consequences of chromosomal instability and copy number variation in humans. Research from patients with MVA, genetically engineered mouse models and functional cellular studies have found the genetic causes to be mutations in components of the spindle-assembly checkpoint as well as in related proteins involved in centrosome dynamics during mitosis. MVA is accompanied by tumour susceptibility (depending on the genetic basis) as well as cellular and systemic stress, including chronic immune response and the associated clinical implications. Mosaic variegated aneuploidy is a rare condition in which the copy number of different chromosomes varies across some cells within an individual. In this Review, the authors discuss the genetic underpinnings and clinical manifestations of this condition and relate these findings to the consequences of chromosomal instability more broadly.