AUTHOR=Panneman Daan M. , Hitti-Malin Rebekkah J. , Holtes Lara K. , de Bruijn Suzanne E. , Reurink Janine , Boonen Erica G. M. , Khan Muhammad Imran , Ali Manir , Andréasson Sten , De Baere Elfride , Banfi Sandro , Bauwens Miriam , Ben-Yosef Tamar , Bocquet Béatrice , De Bruyne Marieke , Cerda Berta de la , Coppieters Frauke , Farinelli Pietro , Guignard Thomas , Inglehearn Chris F. , Karali Marianthi , Kjellström Ulrika , Koenekoop Robert , de Koning Bart , Leroy Bart P. , McKibbin Martin , Meunier Isabelle , Nikopoulos Konstantinos , Nishiguchi Koji M. , Poulter James A. , Rivolta Carlo , Rodríguez de la Rúa Enrique , Saunders Patrick , Simonelli Francesca , Tatour Yasmin , Testa Francesco , Thiadens Alberta A. H. J. , Toomes Carmel , Tracewska Anna M. , Tran Hoai Viet , Ushida Hiroaki , Vaclavik Veronika , Verhoeven Virginie J. M. , van de Vorst Maartje , Gilissen Christian , Hoischen Alexander , Cremers Frans P. M. , Roosing Susanne 

TITLE=Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1112270

DOI=10.3389/fcell.2023.1112270

ISSN=2296-634X

ABSTRACT=<p><bold>Introduction:</bold> 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 &gt;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.</p><p><bold>Methods:</bold> 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 <italic>RPE65</italic> 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.</p><p><bold>Results and discussion:</bold> 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.</p>