2023

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Browsing 2023 by Author "Iqra Arshad"

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    Prioritization and analysis of genetic variations responsible for retinitis pigmentosa
    (UMT, Lhr, 2023) Iqra Arshad
    Inherited retinal disorders (IRDs) encompass a heterogeneous group of genetic conditions affecting the retina, leading to progressive vision loss and, in some cases, blindness. These disorders often emerge during childhood or early adulthood, with common symptoms including night blindness, tunnel vision, and central vision loss. Retinitis Pigmentosa (RP) is an IRD characterized by progressive vision loss due to photoreceptor degeneration, with genetic mutations playing a central role in its pathogenesis. While Congenital stationary night blindness (CSNB) is another rare inherited retinal disorder characterized by impaired night vision and diminished rod cell function, often due to genetic mutations. We selected two families for our study and collected their saliva samples by using NEST kit which were then transported to lab for Whole Exome Sequencing. One individual’s exome from each family was sequenced and one family had unreported novel mutation (766C>T or p.R256X) in SLC24A1 gene. SLC24A1 gene was further studied in detail and analysed by in-sillico tools. Mutations were retrieved from gnomAD and filtered while separate analysis was done for missense and splice site variants. CADD and meta-SNP were used for further selecting pathogenic variants and 55 were declared highly pathogenic. Stability of these pathogenic variants was analysed by different tools like DynaMut, DUET, mCSM and CUPSAT and only 22 were predicted to be destabilising by all the tools. Pathogenicity and functional analysis was predicted by MutPred2 where 42 variants came out to be highly pathogenic. While mutagenesis of these variants was checked using UCSF Chimera and not even single clash was found disturbing the neighbouring zones. Then, we analysed the post translational modification (PTM) sites with ScanProsite and Netsurf and 9 variants were found lying in PTM sites (5 were exposed and on PTM site). Splice Site analysis was done by different bioinformatics tools including SpliceAI, SPiCE, Mutation taster and Human Splice Finder (HSF). And all these tools predicted both of our splice site variants to be pathogenic and disturbing the normal function of SLC24A1.