CEP290

Many variants (also known as mutations) in the CEP290 gene have been found to cause Leber congenital amaurosis. Leber congenital amaurosis is an eye disorder that primarily affects the retina, which is the specialized tissue at the back of the eye that detects light and color. People with this disorder typically have severe visual impairment beginning near birth or shortly afterward. Variants in the CEP290 gene account for 15 to 22 percent of all cases of Leber congenital amaurosis.

A particular genetic change, written as 2991+1655A>G, is the most common CEP290 gene variant associated with Leber congenital amaurosis. This variant creates a  premature stop signal in the instructions for making the CEP290 protein, which reduces the production of functional  protein to low levels in cells. Other CEP290 gene changes responsible for this disorder result in the production of abnormally short, completely nonfunctional versions of the CEP290 protein.

It is unclear how variants in the CEP290 gene cause the characteristic features of Leber congenital amaurosis. A shortage of the CEP290 protein clearly affects the development of the retina. Photoreceptors in the retina contain cilia, which are essential for normal vision. Abnormalities involving these cilia may lead to the severe, early visual impairment characteristic of Leber congenital amaurosis.

MedlinePlus Genetics provides information about Bardet-Biedl syndrome

MedlinePlus Genetics provides information about Joubert syndrome

MedlinePlus Genetics provides information about Meckel syndrome

MedlinePlus Genetics provides information about Senior-Løken syndrome

Several dozen variants in the CEP290 gene have also been identified in other syndromes associated with abnormal cilia. These conditions, which are known as ciliopathies, affect many body systems and include Joubert syndrome, Meckel syndrome, Senior-Løken syndrome, and Bardet-Biedl syndrome (mentioned above). The features of these disorders overlap significantly. They each affect multiple organ systems, most commonly the brain and spinal cord (central nervous system), retina, and kidneys. Meckel syndrome is typically the most severe of the CEP290-associated ciliopathies; affected individuals usually die before or shortly after birth.

The CEP290 gene variants responsible for these disorders lead to the production of an abnormally short version of the CEP290 protein. The abnormal protein likely disrupts cilia function in many different parts of the body. However, it is unclear how variants in this single gene can cause multiple disorders. Researchers speculate that changes in other genes, particularly genes involved in cilia function, may contribute to the varied signs and symptoms of these conditions.