In 2000, a rare mutation at codon 23 causing autosomal dominant retinitis pigmentosa was reported, in which proline was converted to alanine. Several other studies have reported various codon mutations associated with retinitis pigmentosa, including Thr58Arg, Pro347Leu, Pro347Ser, as well as deletion of Ile-255. The codon 23 mutation in the rhodopsin gene, in which proline is changed to histidine, was found to represent the largest fraction of rhodopsin mutations in the United States. One of the main biochemical causes of Retinitis pigmentosa in the case of rhodopsin mutations is protein misfolding and alteration of molecular chaperones. These mutations are found throughout the opsin gene and are distributed throughout the three domains of the protein (the intradiscal, transmembrane, and cytoplasmic domains). To date, up to 150 mutations in the opsin gene associated with Retinitis pigmentosa have been reported since the Pro23 His mutation in the intradiscal domain of the protein was first reported in 1990. Since the discovery of the rhodopsin gene, more than 100 RHO (rhodopsin) gene mutations have been identified, accounting for 15% of all types of retinal degeneration and approximately 25% of the autosomal dominant forms of Retinitis pigmentosa. Mutations in this gene most often present as missense or misfolded mutations of the rhodopsin protein, and most often follow autosomal dominant inheritance patterns.
The rhodopsin gene encodes a major protein for the outer segments of photoreceptors. In 1989, a gene mutation was identified for rhodopsin, a pigment that plays an essential role in the visual transduction cascade that enables vision in low light conditions. The inheritance patterns of Retinitis pigmentosa have been identified as autosomal dominant, autosomal recessive, X-linked, and maternally acquired (mitochondrial), and depend on specific mutations of the Retinitis pigmentosa gene present in the parental generation.
There are multiple genes that, when mutated, can cause the retinitis pigmentosa phenotype.
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