@article{f8ce5e4167864d779c3d5752efcc5b90,
title = "Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis",
abstract = "Introduction: 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.Methods: 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 RPE65 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.Results and discussion: 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.",
keywords = "inherited retinal diseases, targeted gene sequencing, cost-effective, high-throughput, smMIPs, RETINAL DYSTROPHY, MUTATIONS, VARIANTS",
author = "D.M. Panneman and R.J. Hitti-Malin and L.K. Holtes and {de Bruijn}, S.E. and J. Reurink and E.G.M. Boonen and M.I. Khan and M. Ali and S. Andreasson and {De Baere}, E. and S. Banfi and M. Bauwens and T. Ben-Yosef and B. Bocquet and {De Bruyne}, M. and {de la Cerda}, B. and F. Coppieters and P. Farinelli and T. Guignard and C.F. Inglehearn and M. Karali and U. Kjellstrom and R. Koenekoop and {de Koning}, B. and B.P. Leroy and M. McKibbin and I. Meunier and K. Nikopoulos and K.M. Nishiguchi and J.A. Poulter and C. Rivolta and {de la Rua}, E.R. and P. Saunders and F. Simonelli and Y. Tatour and F. Testa and A.A.H.J. Thiadens and C. Toomes and A.M. Tracewska and H.V. Tran and H. Ushida and V. Vaclavik and V.J.M. Verhoeven and {van de Vorst}, M. and C. Gilissen and A. Hoischen and F.P.M. Cremers and S. Roosing",
note = "Funding Information: The authors would like to thank all patients involved and their families for taking part in this research. We thank Saskia D. van der Velde-Visser, Ellen A.W. Blokland, Marlie Jacobs-Camps, Anita Roelofs, Michiel Oorsprong, Marcel Nelen, Simon van Reijmersdal, and Martine van Zweeden, and the Radboud Genomics Technology Center for technical assistance. Sarah De Jaegere (Center for Medical Genetics Ghent Belgium) is thanked for her technical support. We also thank Greg Porreca and Eric Boyden at Molecular Loop Biosciences Inc. for their contribution and expertise. We want to acknowledge the Biobank Nodo Hospital Virgen Macarena (Biobanco del Sistema Sanitario P{\'u}blico de Andaluc{\'i}a) integrated in the Spanish National biobanks Network (PT20/00069) supported by ISCIII and FEDER funds for their collaboration in this work. The work in the Chromosomal Genetics Unit is supported by the CHROMOSTEM research platform. Funding Information: This study received funding from Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This work was supported by grants from Foundation Fighting Blindness Career Development Award CDGE-0621-0809-RAD (SR), Foundation Fighting Blindness project program award PPA-0123-0841-UCL (SR and SdB), Retinitis Pigmentosa Fighting Blindness, Fight for Sight UK (RP Genome Project GR586), Ghent University Special Research Fund (BOF20/GOA/023) (EDB and BL); EJP RD Solve-RET EJPRD19-234 (EDB, BL, SB, CR, FC, and SR). EDB (1802220N) and BL (1803816N) are FWO Senior Clinical Investigators of the Research Foundation Flanders (FWO). EDB, BL, SB, FC, and SR are members of ERN-EYE (Framework Partnership Agreement No. 739534). Funding Information: This study received funding from Novartis. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This work was supported by grants from Foundation Fighting Blindness Career Development Award CDGE-0621-0809-RAD (SR), Foundation Fighting Blindness project program award PPA-0123-0841-UCL (SR and SdB), Retinitis Pigmentosa Fighting Blindness, Fight for Sight UK (RP Genome Project GR586), Ghent University Special Research Fund (BOF20/GOA/023) (EDB and BL); EJP RD Solve-RET EJPRD19-234 (EDB, BL, SB, CR, FC, and SR). EDB (1802220N) and BL (1803816N) are FWO Senior Clinical Investigators of the Research Foundation Flanders (FWO). EDB, BL, SB, FC, and SR are members of ERN-EYE (Framework Partnership Agreement No. 739534). Publisher Copyright: Copyright {\textcopyright} 2023 Panneman, Hitti-Malin, Holtes, de Bruijn, Reurink, Boonen, Khan, Ali, Andr{\'e}asson, De Baere, Banfi, Bauwens, Ben-Yosef, Bocquet, De Bruyne, Cerda, Coppieters, Farinelli, Guignard, Inglehearn, Karali, Kjellstr{\"o}m, Koenekoop, de Koning, Leroy, McKibbin, Meunier, Nikopoulos, Nishiguchi, Poulter, Rivolta, Rodr{\'i}guez de la R{\'u}a, Saunders, Simonelli, Tatour, Testa, Thiadens, Toomes, Tracewska, Tran, Ushida, Vaclavik, Verhoeven, van de Vorst, Gilissen, Hoischen, Cremers and Roosing.",
year = "2023",
month = feb,
day = "3",
doi = "10.3389/fcell.2023.1112270",
language = "English",
volume = "11",
journal = "Frontiers in Cell and Developmental Biology",
issn = "2296-634X",
publisher = "Frontiers Media SA",
number = "1",
}