BEST1 gene
The BEST1 gene provides instructions for making the protein bestrophin-1, which is essential for normal vision and the maintenance of the retina.
Normal Function
The BEST1 gene provides instructions for making a protein called bestrophin-1, which appears to play a critical role in normal vision. Bestrophin-1 is found in a thin layer of cells at the back of the eye called the retinal pigment epithelium. This cell layer supports and nourishes the retina, 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-1 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-1 may also help regulate the entry of charged calcium atoms (calcium ions) into cells of the retinal pigment epithelium.
Health Conditions Related to Genetic Changes
Vitelliform macular dystrophy
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 (Best disease) or the adult-onset form. Both types are characterized by the buildup of a fatty yellow pigment (lipofuscin) in cells of the retinal pigment epithelium, which can eventually damage the photoreceptors critical for sharp central vision.
- Most mutations change single protein building blocks (amino acids) in bestrophin-1.
- The altered protein likely forms an abnormally shaped channel that cannot properly regulate the flow of chloride ions.
Age-related macular degeneration
Mutations in the BEST1 gene have been found in a small number of people with age-related macular degeneration. However, it is not clear if these mutations are involved in the development of the condition, and they are likely not a major risk factor for this common eye disorder.
Autosomal dominant vitreoretinochoroidopathy (ADVIRC)
At least four mutations in the BEST1 gene have been found in individuals with this rare eye disorder. ADVIRC is characterized by abnormalities of the vitreous (the clear gel that fills the eye), the retina, and the choroid (the network of blood vessels within the retina), which can lead to vision impairment.
Retinitis pigmentosa
BEST1 gene mutations have been found in a small number of individuals with eye abnormalities similar to those in retinitis pigmentosa, a group of disorders where photoreceptors gradually deteriorate.
Other disorders
- Glaucoma, cataracts, and nanophthalmos: Mutations in this gene have been linked to increased eye pressure, clouding of the lens, and very small eyes with extreme farsightedness.
- Autosomal recessive bestrophinopathy (ARB): This condition is caused by mutations that alter the structure of bestrophin-1 or prevent its production, leading to progressive vision loss.