Stargardt macular degeneration (Stargardt macular degeneration) - Genes ABCA4 and ELOVL4  

Stargardt Macular degeneration is an eye genetic alteration that causes progressive loss of vision. This disease affects the retina, specifically the macula. The macula is responsible for sharp central vision, which is required for detailed tasks such as reading, driving and recognizing faces. In most people with macular degeneration Stargardt lipofuscin accumulates 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. In addition to the loss of central vision, the people affected have problems with night vision. Some affected individuals also have impaired color vision. Signs and symptoms of macular degeneration Stargardt usually occur from late childhood to adulthood and worsen over time.

In most cases, this process is due to mutations in the ABCA4 gene. Less commonly, the disease is due to mutations in the gene ELOVL4. These genes encode proteins found in photoreceptors.

The ABCA4 gene, located on the short arm of chromosome 1 (1p22), encodes a protein that carries potentially toxic to the outside of photoreceptor cells substances. Specifically, removes N-retiniliden-PE. These substances are formed after phototransduction. They have identified more than 640 mutations in the gene ABCA4 responsible for Stargardt macular degeneration. Most of these mutations consist of amino acid changes in protein ABCA4. Mutations in ABCA4 gene prevents the ABCA4 protein eliminate toxic byproducts of photoreceptor cells. These toxic substances accumulate and form lipofuscin in the photoreceptor cells and surrounding retinal cells, ultimately leading to cell death. The loss of retinal cells results in the progressive loss of vision characteristic of Stargardt macular degeneration. They described several genetic mutations ABCA4 responsible for various forms of vision loss in different individuals. It is unclear how mutations in the ABCA4 gene can result in different ocular disorders.

The ELOVL4 gene, located on the long arm of chromosome 6 (6q14), encodes a protein that plays a fatty acid formation of very long chain paper. The ELOVL4 protein is primarily expressed in the retina, but is also expressed in the brain and skin. In the retina, ELOVL4 protein occurs in the photoreceptors. Within photoreceptor cells, this protein is found in the endoplasmic reticulum, involved in the production, processing and transport of proteins. They have identified at least three mutations in the gene ELOVL4 result Stargardt macular degeneration. These mutations create a premature stop signal coding ELOVL4 protein. Mutations in the gene ELOVL4 lead to clumping ELOVL4 proteins which may interfere with cellular functions of the retina and, ultimately, lead to cell death. Loss of photoreceptor cells leads to progressive vision loss in people with Stargardt macular degeneration.

When the disease is due to mutations in the ABCA4 gene is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. Meanwhile, when the disease is due to mutations in the ELOVL4 gene is inherited in an autosomal dominant pattern, which means that a copy of the altered gene in each cell is sufficient to express the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with macular degeneration Stargardt by complete PCR amplification of the exons of ABCA4 and ELOVL4 genes, respectively, and subsequent sequencing. We recommend starting the study by exons of ABCA4 gene responsible for most cases of the disease, thus saving time and cost involved in most cases. If not, it is suggested to continue the study by exons of the gene ELOVL4.

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).