Vitelliform macular dystrophy (vitelliform macular dystrophy) - Genes BEST1 and PRPH2.

Macular dystrophy is a genetic Vitelliform eye disorder that can lead to progressive loss of vision. This alteration affects the retina, specifically cells of the macula responsible for sharp central vision. Vitelliform macular dystrophy causes lipofuscin accumulation in the underlying cells of the macula. Eventually, the abnormal accumulation of this substance can damage the cells that are critical for clear central vision. As a result, those affected often lose their central vision, and vision may be blurred or distorted. This disorder usually does not affect peripheral vision or night vision.

They described two forms of vitelliform macular dystrophy with similar characteristics. Early - onset form (known as Best disease), usually appears in childhood. The onset of symptoms and the degree of vision loss vary widely. Onset of the adult form starts later, usually in mid-adulthood, and tends to cause progressive loss of vision. Each of the forms of vitelliform macular dystrophy has characteristic changes in the macula which can be detected during an eye examination.

This process is due to mutations in genes BEST1 or PRPH2.

The BEST1 gene, located on the long arm of chromosome 11 (11q13), encodes a protein called bestrophin-1, plays an important role in normal vision. This protein is found in the retinal pigment epithelium. This layer of cells supports and nourishes the retina. The retinal pigment epithelium is involved in the growth and development of the eye, the retina maintenance, and normal function of photoreceptors. This protein acts as a channel that controls movement of chloride ions inside or outside the cells in the retina. There are more than 100 mutations in the gene BEST1 in people with macular dystrophy Vitelliform. These mutations can lead to early onset form of the disease (known as Bests disease) or late - onset form. Most mutations change the amino acids in bestrophin-1. Altered protein, probably forms a channel abnormally can not properly regulate the flow of chloride ions inside or outside the cells in the pigment epithelium retina.No clear how the malfunction of these channels it is related to the accumulation of lipofuscin in the macula and progressive loss of vision.

The PRPH2 gene, located on the short arm of chromosome 6 (6p21.1), encodes a protein called peripherin-2, which plays an important role in normal vision. Peripherin-2 is in the retina. This protein is essential for normal function of photoreceptors. Within these cells, peripherin-2 is involved in the formation and stability of structures containing sensitive pigments to light. Mutations in the gene PRPH2 are responsible for some cases of macular dystrophy Vitelliform adult onset. Most mutations change the amino acids in peripherin-2. These mutations alter the structure of the protein or coding result of an abnormally short, nonfunctional version of the protein. When peripherin-2 is altered, or is absent, the photoreceptors degenerate over time. This loss of photoreceptors underlying abnormalities of the retina and progressive vision loss characteristic of macular dystrophy Vitelliform. It is unclear why mutations in the gene PRPH2 affect only the central vision in people with the disease.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for alteration is expressed. In most cases, an affected person has a parent with the disorder. The inheritance pattern of vitelliform macular dystrophy adult is uncertain. It is believed that this disorder can be inherited in an autosomal dominant pattern. However, it s hard to be sure because many people affected have no history of the disease in his family, and has only been reported in a small number of families affected.

Tests in IVAMI: in IVAMI perform detection of mutations associated with vitelliform macular dystrophy, by complete PCR amplification of the exons of the BEST1 and PRPH2 genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).