OCRL

The OCRL gene provides instructions for making an enzyme that is present in cells throughout the body. This enzyme helps modify fat (lipid) molecules called membrane phospholipids, which form the basic structure of cell membranes. Specifically, the OCRL enzyme acts on a group of membrane phospholipids known as phosphoinositides.

Within cells, the OCRL enzyme is concentrated in a complex network of membranes known as the trans-Golgi network. This structure sorts proteins and other molecules and sends them to their intended destinations inside or outside the cell. The OCRL enzyme is also found on endosomes, compartments that are formed at the cell surface to carry proteins and other molecules to their destinations within the cell.

By controlling the level of phosphoinositides, the OCRL enzyme helps regulate the transport of certain substances to and from the cell membrane. The enzyme may also be involved in the regulation of the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move.

Lowe syndrome - caused by mutations in the OCRL gene

More than 120 mutations in the OCRL gene have been identified in individuals with Lowe syndrome. Some of these mutations prevent the production of any OCRL enzyme. Other mutations reduce or eliminate the activity of the enzyme or prevent it from interacting with other proteins within the cell. These changes impact signaling within cells, the transport of certain molecules, and regulation of the actin cytoskeleton.

Researchers are working to determine how OCRL mutations cause the characteristic features of Lowe syndrome. In the brain, defects in the transport of critical proteins to and from the cell surface may disrupt communication between nerve cells, causing developmental delay and intellectual disability. In the kidneys, loss of OCRL enzyme activity may impair the transport of proteins needed for the reabsorption of important nutrients into the bloodstream.

Because the OCRL enzyme is present throughout the body, it is unclear why the medical problems associated with Lowe syndrome are mostly limited to the brain, kidneys, and eyes. It is possible that other enzymes may be able to compensate for the defective OCRL enzyme in unaffected tissues.

other disorders - caused by mutations in the OCRL gene

Mutations in the OCRL gene are also responsible for a condition called Dent disease. This disorder is characterized by kidney abnormalities similar to those seen in Lowe syndrome. Unlike Lowe syndrome, however, Dent disease does not affect the eyes or brain. The reason for this difference is unknown.

Mutations in the OCRL gene have been identified in only a few families with Dent disease. Most cases of this condition are caused by mutations in another gene, CLCN5. Researchers suspect that the proteins produced from the OCRL and CLCN5 genes may cooperate in a shared function in the kidney.