| dc.description.abstract | Mosaic variegated aneuploidy (MVA) is a rare autosomal recessive disorder characterized by constitu-tional mosaic aneuploidies of multiple chromosomes and tissues. MVA is associated with a broad range of symptoms and genetic and clinical heterogeneity among its patients, which has complicated the identification of a molecular basis underlying this disease. So far, mutations in two proteins have been implicated in causing MVA: BUBR1, an essential component of the spindle assembly checkpoint; and CEP57, a centrosome protein important for microtubule and centriole stability. Although both proteins are required for faithful chromosome segregation, they also play roles in other processes: BUBR1 coun-ters ageing and affects cilia formation, a process that requires centrosomes and thus likely also involves CEP57. In this article I review the theories of aneuploidy, ageing and defective cilia as causes for MVA, and describe a potential link between cilia and ageing that could explain the molecular origin of MVA and its broad and heterogeneous phenotype. | |
