Study on the Abnormalities in the Genetic Sequence in DNA Causing Leber Congenital Amaurosis (LCA)

RPE65 is a gene critical for the visual function. Its mutation disrupts the vertebrate visual cycle, resulting in eye disorders such as RP and LCA. The role of RPE65 in the visual cycle is to catalyze the transformation of all-trans-retinyl ester to 11-cis-retinol and to allow the eye to detect light. [1] In LCA, a defective RPE65 gene results in a decreased regeneration of 11-cis-retinal. This breaks the phototransduction pathway and photoreceptors are unable to respond to light. Although malfunction of RPE65 causes LCA and RP eye disorders, research has shown that partial inhibition of RPE65 may treat age-related macular degeneration (AMD).

This paper identifies and analyzes abnormalities in the genetic sequence that lead to mutations in patients with genetic eye disorders. In this paper, computational analysis of Arg91Trp mutation was performed to determine its resulting pathogenesis. First, sequence abnormalities in the gene of RP and LCA patients were identified. Then, sterochemical analysis was performed via gene editing program and molecular geometry analysis to observe the effect of the mutation on the peptide’s thermodynamic stability.