2.1. Mosaic Variegated Aneuploidy Syndrome

More than a dozen mutations in the BUB1B gene have been found to cause mosaic variegated aneuploidy (MVA) syndrome type 1. This condition is characterized by cells with abnormal numbers of chromosomes, a situation known as aneuploidy. Affected individuals grow slowly and have an unusually small head size (microcephaly) and an increased risk of developing cancer in childhood.

MVA syndrome type 1 occurs when both copies of the BUB1B gene have mutations. These mutations reduce the amount of BUBR1 protein in cells or impair the protein's ability to function. A shortage of functioning BUBR1 protein leads to errors in the distribution of chromatids during cell division. Without BUBR1 protein, cell division can proceed, even if all the chromatids are not attached to spindle microtubules. Unattached chromatids are not positioned correctly for separation, and the resulting cells have abnormal numbers of chromosomes.

Research suggests that impairment of the process that delays cell division until the correct time underlies the increased risk of cancer in MVA syndrome, although the mechanism is not completely understood. It is also unclear how BUB1B gene mutations or aneuploidy leads to the other features of MVA syndrome. Researchers speculate that the abnormal cells undergo self-destruction (apoptosis). The signs and symptoms of MVA syndrome may be due to the loss of cells from various tissues during early development.

2.2. Other Disorders

Mutations in the BUB1B gene can also cause a related problem with chromosomes called premature chromatid separation trait. Although individuals with this trait have chromosome abnormalities that indicate trouble with normal chromosome separation during cell division, affected individuals usually have no health problems related to the trait. This trait occurs in individuals with a genetic change in one of the two copies of the BUB1B gene.