BEST1

The BEST1 gene provides instructions for making a protein called bestrophin. Although the exact function of this protein is unknown, it appears to play a critical role in normal vision. Bestrophin is found in a thin layer of cells at the back of the eye called the retinal pigment epithelium (RPE). This cell layer supports and nourishes the retina, which is the light-sensitive tissue that lines the back of the eye. The retinal pigment epithelium is involved in the growth and development of the eye, maintenance of the retina, and the normal function of specialized cells called photoreceptors that detect light and color.

Bestrophin functions as a channel across cell membranes in the retinal pigment epithelium. Charged chlorine atoms (chloride ions) are transported through these channels in response to cellular signals. Some studies suggest that bestrophin may also help regulate the entry of charged calcium atoms (calcium ions) into cells of the retinal pigment epithelium. Other potential functions of bestrophin are under study.

vitelliform macular dystrophy - caused by mutations in the BEST1 gene

More than 100 mutations in the BEST1 gene have been identified in people with vitelliform macular dystrophy. These mutations can cause either the early-onset form of the disorder (known as Best disease) or the adult-onset form. Both types of vitelliform macular dystrophy are characterized by the buildup of a fatty yellow pigment (lipofuscin) in cells of the retinal pigment epithelium. Over time, the abnormal accumulation of this substance can damage the photoreceptors that are critical for sharp central vision.

Most BEST1 mutations change or delete single protein building blocks (amino acids) in bestrophin. The altered protein probably forms an abnormally shaped channel that cannot properly regulate the flow of chloride ions into or out of cells in the retinal pigment epithelium. It remains unclear how this defect is related to the buildup of lipofuscin and a progressive loss of central vision in people with vitelliform macular dystrophy.

other disorders - caused by mutations in the BEST1 gene

BEST1 mutations cause several additional eye disorders. For example, mutations in this gene have been found in some cases of a rare condition called autosomal dominant vitreoretinochoroidopathy (ADVIRC). This condition is characterized by abnormalities of the retina and the clear gel that fills the eyeball (the vitreous). Mutations in the BEST1 gene also have been identified in individuals who have other eye abnormalities, such as very small eyes (nanophthalmos), increased pressure in the eyes (glaucoma), and clouding of the lens (cataracts). Although it is not known how BEST1 mutations cause these problems, researchers believe that the eye abnormalities are related to defects in the retinal pigment epithelium.

A recently described eye disorder called autosomal recessive bestrophinopathy is also caused by mutations in the BEST1 gene. This condition is characterized by progressive vision loss and an autosomal recessive inheritance pattern. Autosomal recessive inheritance means affected individuals have mutations in both copies of the BEST1 gene in each cell. The mutations that cause autosomal recessive bestrophinopathy alter the structure of bestrophin, which obstructs the flow of chloride ions into or out of cells of the retinal pigment epithelium. It is unclear how changes in bestrophin lead to vision loss in people with this disorder.

Additionally, researchers have studied BEST1 mutations related to age-related macular degeneration. This eye disease is a leading cause of vision loss among older people worldwide. Mutations in the BEST1 gene have been found in a small number of people with age-related macular degeneration, but changes in this gene are probably not a major risk factor for this common eye disorder. A combination of genetic and environmental factors likely determine the risk of developing age-related macular degeneration.