2.1. Mosaic variegated aneuploidy syndrome

At least two TRIP13 gene mutations have been found to cause mosaic variegated aneuploidy (MVA) syndrome. This condition is typically characterized by cells with abnormal numbers of chromosomes, a situation known as aneuploidy. Individuals with MVA syndrome caused by TRIP13 gene mutations have a high risk of developing a form of kidney cancer called Wilms tumor in childhood. They may also grow slowly and have an unusually small head size (microcephaly).

TRIP13 gene mutations involved in MVA syndrome lead to production of an abnormally short protein that is quickly broken down. As a result, cells lack TRIP13 protein. A shortage of this protein impairs the spindle assembly checkpoint, and cell division proceeds, even if not all the chromatids are attached to spindle microtubules. Unattached chromatids are not positioned correctly for separation, and the resulting cells often have abnormal numbers of chromosomes. Some people with TRIP13 gene mutations have chromosome abnormalities that indicate problems with chromatid separation, although they do not have abnormal numbers of chromosomes in their cells. These individuals have the other signs and symptoms of MVA syndrome.

Research suggests that problems with the spindle assembly checkpoint underlie the development of cancer in MVA syndrome, although the mechanism is not completely understood. It is also unclear how TRIP13 gene mutations lead to 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.