c.۵۲۴۴ del G: A Novel Mutation in the ABCA۴ Gene is Associated with Retinitis Pigmentosa

Background: Retinitis pigmentosa (RP) is an inherited retinal disease that affects approximately ۱ in۳,۵۰۰ individuals worldwide. It is characterized by progressive degeneration of photoreceptor cells,leading to visual impairment and eventual blindness. RP exhibits significant genetic heterogeneity, withmutations identified in over ۷۰ genes associated with the disease. The ABCA۴ gene has beenextensively studied due to its involvement in various retinal dystrophies, including Stargardt diseaseand cone-rod dystrophy. ]۱[Methods: In this study, we obtained blood samples from a RP patient with characteristic symptomssuch as night blindness and peripheral vision loss. Genomic DNA was extracted using standardprotocols, followed by whole exome sequencing (WES) technique. Data analysis of WES wasperformed based on a specific gene panel including known RP-associated genes. The resulting sequencedata was analyzed using bioinformatics tools to identify potential disease-causing variants, which wasconfirmed by Sanger sequencing. The secondary structure of normal and mutant mRNA was analyzedby the RNA fold database .Results: WES analysis revealed a homozygous variant reported as a likely pathogen in Franklin andVarSome; However, there is no evidence related to it in Clinvar. This novel mutation, c.۵۲۴۴ del G inexon ۳۷ of the ABCA۴ gene, is a frameshift variation leads to a premature stop codon downstream,resulting in a short mRNA and a truncated protein product. The secondary structure of mRNA waschanged after the mentioned mutation, which could affect its downstream functions .Discussion and conclusion: The ABCA۴ gene encodes an ATP-binding cassette transporter involved intransporting retinoids across photoreceptor outer segments' disc membranes [۲]. Mutations affectingthis gene have been associated with impaired clearance of toxic retinoid derivatives, leading tophotoreceptor cell death [۳]. In conclusion, the identification of this novel mutation (c.۵۲۴۴ del G) andcomparison of the secondary structure of the normal and mutant mRNA expands our understanding ofthe genetic landscape underlying RP and highlights the importance of comprehensive genetic testingfor accurate diagnosis and prognosis prediction.

کلیدواژه ها:

WES ، ABCA۴ gene ، Retinitis pigmentosa ، mRNA secondary structure