VLDLR

The VLDLR gene provides instructions for making a protein called a very low density lipoprotein (VLDL) receptor. This protein is active in many different organs and tissues, including the heart, muscles used for movement (skeletal muscles), fatty (adipose) tissue, and the kidneys. The VLDL receptor appears to play a particularly important role in the developing brain.

The VLDL receptor works together with a protein called reelin. Reelin fits into the VLDL receptor like a key in a lock, which triggers a series of chemical reactions within the cell. During early brain development, the reelin signaling pathway helps to guide the movement of immature nerve cells (neuroblasts) to their appropriate locations in the brain.

VLDLR-associated cerebellar hypoplasia - caused by mutations in the VLDLR gene

At least six mutations in the VLDLR gene have been found to cause VLDLR-associated cerebellar hypoplasia. These mutations prevent cells from producing any functional VLDL receptor protein. Without this protein, neuroblasts cannot reach the parts of the brain where they are needed. These problems with brain development predominantly affect the cerebellum, which is the part of the brain that coordinates movement. People with VLDLR-associated cerebellar hypoplasia have an unusually small and underdeveloped cerebellum, which leads to problems with balance and coordination (ataxia) and impaired speech. Other regions of the brain are also affected, resulting in intellectual disability and the other major features of this condition.