Photoreceptor Gene Defects Causing Retinal Degeneration
Gene mutations involving the phototransduction pathway lead to inherited retinal dystrophies with varying degrees of visual impairment. These mutations can disrupt physiology in different ways; they can alter the transduction cascade, protein folding, or localization of the affected protein. Retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), and Stargardt disease are among the most prevalent inherited retinal dystrophies. Autosomal dominant RP (ADRP) can be caused by more than 100 different mutations in the rhodopsin gene (RHO). The most common RHO mutation is P23H (responsible for 10% of RP cases in the United States), which causes the rhodopsin protein not to fold properly and instead to accumulate in the rough endoplasmic reticulum. Generally, RHO mutations affecting the intradiscal area and amino-terminal end of rhodopsin result in less severe defects than do mutations affecting the cytoplasmic region and the carboxyl tail. Alterations in the middle of the gene, coding for the transmembrane regions of rhodopsin, result in moderately severe defects. Relatively uncommon mutations have been reported in the rhodopsin gene that cause autosomal recessive RP (ARRP) and a stationary form of nyctalopia. See Tables 12-1 through 12-4 for other gene mutations that cause inherited retinal dystrophies.
Table 12-1 Rod-Specific Gene Defects
Table 12-2 Cone- and Rod-Specific Gene Defects
Table 12-3 Cone-Specific Gene Defects
Table 12-4 Ubiquitously Expressed Genes Causing Retinal Degeneration
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.