Contributing+Genes

Etiology There are over 50 genes that are known to cause RP, so it is sometimes difficult to pinpoint the culprit. With that said there are a couple that are more prevalent within each group. The most well known is the RHO gene, which causes the disease by means of autosomal dominance. It makes up about 20-30% in this category of RP. The most common from the next group, autosomal recessive, is the gene USH2A, which makes up about 10-15% in this mode of inheritance. Finally the most common one from the x-linked mode of inheritance is RPGR. At 70-90% this gene makes up a much larger portion of it's group (Fahim, Daiger, Weleber, 2013.)
 * What genes cause Retinitis Pigmentosa?**

__**RHO**__ The rhodopsin gene is responsible for the synthesis of the protein rhodopsin. A little more than 130 mutations in the RHO gene have been discovered that lead to autosomal dominant retinitis pigmentosa. After being synthesized in the rough ER the protein makes its way to the plasma membrane where it forms a vesicle using the membrane. Once the it makes its way through the plasma membrane it stays membrane bound to the rod cell that synthesized it (McKeone, Wikstrom¸ Kiel, Rakoczy, 2014.) The protein contains a light sensitive molecule called a chromophore in the center that starts a chain reaction to allow a signal to be sent to the brain. The chromophore in rhodopsin is 11-cis-retinol (Opefi, South, Reynolds, Smith, Reeves, 2013.) Mutations to the RHO can range from the transport of the molecule to the functionality of the protein. When mutations for this protein protein were discovered classes were made to differentiate them. Class I mutations involve just the transport to the membrane of the cell. Class II mutations accumlate poorly on the surface of the cell, regenerate with the chromophore incorrectly, and are not transported correctly as well. Class III affects the endocytosis that helps transport the protein across the membrane. Class IV affects the opsin subunit.Opsin is a subunit that helps make up rhodopsin. In class IV mutations, the stability of opsin is affected and post translational modifications that are supposed to occur do not. Class V involves an increased activity of the molecule called transducin, which is a G- protein activated after light has activated the rhodopsin. The last class, class VI, include mutations that affect opsin activation (McKeone, Wikstrom¸ Kiel, Rakoczy, 2014.) Even with this classification system there are so many different problems, which could make for a difficult time when developing remedies.
 * Location**: 3q21-q24

__**USH2A**__ This gene is responsible for the synthesis of a protein called usherin. This protein helps make up basement membranes, which are stacks of thin sheets that support certain tissues. These basement membranes are found in a lot of tissues in the body, so mutations to this gene do not just affect sight (US National Library of Medicine, 2014.) The name of the actual disease is usher syndrome. Retinitis pigmentosa is merely a loss of sight that accompanies hearing loss in this disease. This form of RP is considered syndromic because it come from a syndrome and not from gene mutations that directly cause RP (Méndez-Vidal, González-del Pozo, Vela-Boza, Santoyo-López, López-Domingo, Vázquez-Marouschek, Antiñolo, 2013.) The reason for loss of sight and the loss of hearing is due to the fact that the protein is located in the membranes of the inner ear and in the light sensitive membranes of the retina. The actual function of the protein is not well known, but it is theorized that the protein is involved in retinal and inner ear development. More specifically it is thought that it helps facilitate cell to cell communication at synapses. It would make sense that this protein has involvement during development because this form of RP is seen in patients that have not even reached their teens. There are over 200 mutations that have been recorded for the gene and only some of these affect the functionality of the eye. Most of the time mutations that lead to autosomal recessive retinitis pigmentosa are due a single amino acid mutation that doesn't allow for the protein to function correctly (US National Library of Medicine, 2014.)
 * Location**: 1q41

__**RPGR**__ Since this gene is x- linked this form of RP primarilt affects males, but there are special cases where females are affected as well. RPGR codes for a protein that in found within cilia throughout the body. The mutation that affects the cilia within the retina is usually on the exon ORF15. About 60% of the disease causing mutation are found on this exon. The reason for this is that this exon has a code that is very repetitive and purine rich. This repetitive code allows for slipped strand mispairing, which is when the correct bases do not match up. A mutation to this area does not allow for the retinal cilia to traffic proteins correctly. Once again it is not really known how the dysfunction of the cilia cause the gradual loss of photoreceptors (Yang, Yin, Feng, You, Wu, Chen, Ma, 2014.) .
 * Location**: Xp21.1

Home Diagnosis/Treatment Research/Conclusions References