2.1. Grange syndrome

At least five mutations in the YY1AP1 gene have been identified in people with Grange syndrome. This rare condition causes narrowing (stenosis) and blockage (occlusion) of blood vessels that supply blood to many organs and tissues, including the kidneys, brain, and heart. Grange syndrome can also be associated with short fingers and toes (brachydactyly), fusion of some of the fingers or toes (syndactyly), fragile bones that are prone to breakage, learning disabilities, and heart defects.

Mutations in the YY1AP1 gene are described as "loss-of-function" because they prevent the production of any functional YY1AP1 protein. A loss of this protein disrupts the function of the INO80 chromatin remodeling complex, which alters the activity of multiple genes in smooth muscle cells. Researchers suspect that these changes in gene expression lead to reduced cell proliferation and differentiation. However, it is unclear how these changes cause narrowing and blockage of arteries. It is also unknown how YY1AP1 gene mutations are related to other features of Grange syndrome, such as bone abnormalities and learning disabilities.