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

• DOI: 10.3389/fcell.2023.1112270
• Publication Date: 2023-02-03T06:21:40Z
• Authors: Daan M. Panneman; Rebekkah J. Hitti...; Lara K. Holtes; Suzanne E. de Bruijn; Janine Reurink; Erica G. M. Boonen; Muhammad Imran Khan; Manir Ali; Sten Andréasson; Elfride De Baere; Sandro Banfi; Miriam Bauwens; Tamar Ben-Yosef; Béatrice Bocquet; Marieke De Bruyne; Berta de la Cerda; Frauke Coppieters; Pietro Farinelli; Thomas Guignard; Chris F. Inglehearn; Marianthi Karali; Ulrika Kjellström; Robert Koenekoop; Bart de Koning; Bart P. Leroy; Martin McKibbin; Isabelle Meunier; Konstantinos Niko...; Koji M. Nishiguchi; James A. Poulter; Carlo Rivolta; Enrique Rodríguez...; Patrick Saunders; Francesca Simonelli; Yasmin Tatour; Francesco Testa; Alberta A. H. J. ...; Carmel Toomes; Anna M. Tracewska; Hoai Viet Tran; Hiroaki Ushida; Veronika Vaclavik; Virginie J. M. Ve...; Maartje van de Vorst; Christian Gilissen; Alexander Hoischen; Frans P. M. Cremers; Susanne Roosing
• Keywords: Proband; ABCA4; RPE65

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by cone retina. A genetic diagnosis for IRDs is challenging since >280 genes associated with these conditions. While whole exome sequencing (WES) commonly used diagnostic facilities, costs required infrastructure prevent its global applicability. Previous studies have shown cost-effectiveness sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort patients diagnosed Stargardt disease other maculopathies. Methods: Here, we introduce smMIPs panel that targets exons splice sites all currently known RP LCA, entire RPE65 gene, causative deep-intronic variants leading to pseudo-exons, part RP17 region autosomal dominant RP, total 16,812 smMIPs. The RP-LCA was screen 1,192 probands from an international predominantly LCA cases. Results discussion: After analysis, yield 56% obtained which on par results WES analysis. effectiveness reduced compared renders competitive approach provide IRD diagnosis, especially countries restricted access testing.