ANKH

The ANKH gene provides instructions for making a protein that is present in bone. This protein transports a molecule called pyrophosphate out of cells to the intricate network of proteins that forms in the spaces between cells (extracellular matrix). Pyrophosphate helps regulate bone formation by preventing mineralization, the process by which minerals such as calcium and phosphorus are deposited in developing bones. The ANKH protein may have other, unknown functions.

craniometaphyseal dysplasia - caused by mutations in the ANKH gene

At least seven mutations in the ANKH gene have been found to cause craniometaphyseal dysplasia. Some mutations change a single protein building block (amino acid) in the ANKH protein, whereas others insert or delete an amino acid in the ANKH protein. These mutations most likely decrease the protein's ability to transport pyrophosphate out of cells. Reduced levels of pyrophosphate increase bone mineralization, which may contribute to the bone overgrowth seen in craniometaphyseal dysplasia.

other disorders - associated with the ANKH gene

About five mutations in the ANKH gene have been found to cause a rare hereditary form of calcium pyrophosphate dihydrate deposition disease (CPPDD). CPPDD, also called chondrocalcinosis or pseudogout, is characterized by the accumulation of calcium pyrophosphate dihydrate crystals in the cartilage of joints. The buildup of these crystals weakens cartilage and causes it to break down more easily. The crystals may cause pain and inflammation in the joints. Most cases of CPPDD occur in people older than 40, are not inherited, and have an unknown cause.

Mutations in the ANKH gene have been shown to cause CPPDD in a few families. In these families, one altered copy of the ANKH gene in each cell is sufficient to cause the condition. Individuals with familial CPPDD caused by ANKH mutations typically form crystal deposits within multiple joints during early adulthood. Researchers believe that these mutations lead to elevated pyrophosphate levels in the extracellular matrix. High levels of pyrophosphate result in excessive formation of calcium pyrophosphate dihydrate crystals within joints.

Studies suggest that certain variations (polymorphisms) in the ANKH gene are associated with the normal difference in bone size and shape among individuals. These polymorphisms probably result in slight changes in the activity of the ANKH protein, affecting the levels of pyrophosphate in the extracellular matrix.