Genomics of Retinal Degenerations


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PhD thesis: a PhD thesis.
Genomics of Retinal Degenerations
Peter Virginie
Stamenkovic Ivan
Rivolta Carlo
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Université de Lausanne, Faculté de biologie et médecine
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Visual perception relies on integrity of the retina, where light-induced signals from millions of photoreceptors are initially processed and transmitted to the brain. lt is this function which is lost in inherited retinal disease (IRD), a common cause of lifelong visual impairment or blindness. IRD is caused by the presence of DNA mutations in one of the 270 genes already discovered or those remaining to be identified. Today, finding the genetic causality of all forms of IRD is needed in order to establish an accurate diagnosis in ail patients and enable progress toward development of treatments. lndeed, research is revolutionizing our understanding of the mechanisms responsible for vision loss, creating opportunities for therapeutic interventions during the course of disease. This thesis aims toward this objective, through systematically characterizing !RD-patient cohorts from different regions of the world: Switzerland, Sweden, Portugal, and Pakistan. Our results expand the spectrum of variants and genes associated with IRD and describe the phenotypes elicited by the mutations reported. Specifically, we establish the first study assessing the genotype-phenotype landscape of IRDs in the Portuguese population, revealing the presence of prevalent and population­ specific mutational events for this part of Europe. Additionally, new genotype-phenotype associations were ascertained, related to the genes ARL2BP, ARSG, and INPPSE. Finally, a navel disease gene, P/50, was implicated in the pathogenesis of a multisystemic disorder described in this work. ln conclusion, our findings provide new scientific insights to better diagnose patients affected with IRD and reveal new pathways involved in vision loss. Thereby, the management of these disorders will be improved, and the development of new therapies accelerated.
Create date
22/02/2021 12:18
Last modification date
23/02/2021 7:26
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