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Article Abstract
Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9936074 | PMC |
| http://dx.doi.org/10.3389/fcell.2023.1112270 | DOI Listing |
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Article Synopsis
- Macular dystrophies are inherited retinal disorders that lead to central vision loss and are identified as rare individually but common overall.
- A specialized genetic testing method called Single molecule Molecular Inversion Probes (smMIPs) was successfully used to analyze 57 cases of macular dystrophy in the UK, revealing a high solve rate of 63.2%.
- The study found that most variants in Caucasian STGD1 cases are well-known, and it established that associated diseases can often be differentiated from other macular dystrophies through thorough clinical evaluation.