What are the genetic changes related to familial idiopathic basal ganglia calcification ?
Mutations in the SLC20A2 gene cause nearly half of all cases of FIBGC. A small percentage of cases are caused by mutations in the PDGFRB gene. Other cases of FIBGC appear to be associated with changes in chromosomes 2, 7, 9, and 14, although specific genes have yet to be identified. These findings suggest that multiple genes are involved in this condition.  The SLC20A2 gene provides instructions for making a protein called sodium-dependent phosphate transporter 2 (PiT-2). This protein plays a major role in regulating phosphate levels within the body (phosphate homeostasis) by transporting phosphate across cell membranes. The SLC20A2 gene mutations that cause FIBGC lead to the production of a PiT-2 protein that cannot effectively transport phosphate into cells. As a result, phosphate levels in the bloodstream rise. In the brain, the excess phosphate combines with calcium and forms deposits.  The PDGFRB gene provides instructions for making a protein that plays a role in turning on (activating) signaling pathways that control many cell processes. It is unclear how PDGFRB gene mutations cause FIBGC. Mutations may alter signaling within cells that line blood vessels in the brain, causing them to take in excess calcium, and leading to calcification of the lining of these blood vessels. Alternatively, changes in the PDGFRB protein could alter phosphate transport signaling pathways, causing an increase in phosphate levels and the formation of calcium deposits.  Researchers suggest that calcium deposits lead to the characteristic features of FIBGC by interrupting signaling pathways in various parts of the brain. Calcium deposits may disrupt the pathways that connect the basal ganglia to other areas of the brain, particularly the frontal lobes. These areas at the front of the brain are involved in reasoning, planning, judgment, and problem-solving. The regions of the brain that regulate social behavior, mood, and motivation may also be affected.  Research has shown that people with significant calcification tend to have more signs and symptoms of FIBGC than people with little or no calcification. However, this association does not apply to all people with FIBGC.