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.

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Item Type:	Article
Authors/Creators:	Panneman, DM Hitti-Malin, RJ Holtes, LK de Bruijn, SE Reurink, J Boonen, EGM Khan, MI Ali, M https://orcid.org/0000-0003-3204-3788 Andréasson, S De Baere, E Banfi, S Bauwens, M Ben-Yosef, T Bocquet, B De Bruyne, M de la Cerda, B Coppieters, F Farinelli, P Guignard, T Inglehearn, CF https://orcid.org/0000-0002-5143-2562 Karali, M Kjellström, U Koenekoop, R de Koning, B Leroy, BP McKibbin, M Meunier, I Nikopoulos, K Nishiguchi, KM Poulter, JA Rivolta, C Rodríguez de la Rúa, E Saunders, P Simonelli, F Tatour, Y Testa, F Thiadens, AAHJ Toomes, C https://orcid.org/0000-0001-8373-9545 Tracewska, AM Tran, HV Ushida, H Vaclavik, V Verhoeven, VJM van de Vorst, M Gilissen, C Hoischen, A Cremers, FPM Roosing, S
Copyright, Publisher and Additional Information:	© 2023 Panneman, Hitti-Malin, Holtes, de Bruijn, Reurink, Boonen, Khan, Ali, Andréasson, De Baere, Banfi, Bauwens, Ben-Yosef, Bocquet, De Bruyne, Cerda, Coppieters, Farinelli, Guignard, Inglehearn, Karali, Kjellström, Koenekoop, de Koning, Leroy, McKibbin, Meunier, Nikopoulos, Nishiguchi, Poulter, Rivolta, Rodríguez de la Rúa, Saunders, Simonelli, Tatour, Testa, Thiadens, Toomes, Tracewska, Tran, Ushida, Vaclavik, Verhoeven, van de Vorst, Gilissen, Hoischen, Cremers and Roosing. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords:	inherited retinal diseases, targeted gene sequencing, cost-effective, high-throughput, smMIPs
Dates:	Published: 3 February 2023 Published (online): 3 February 2023 Accepted: 20 January 2023
Institution:	The University of Leeds
Funding Information:	Funder Grant number Fight for Sight GR586 Retina UK was Retinitis Pigmentosa Fighting Blindn 557464
Depositing User:	Symplectic Publications
Date Deposited:	28 Feb 2023 14:59
Last Modified:	28 Feb 2023 15:44
Status:	Published
Publisher:	Frontiers Media
Identification Number:	10.3389/fcell.2023.1112270
Related URLs:	PubMed URL
Open Archives Initiative ID (OAI ID):	oai:eprints.whiterose.ac.uk:196829

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

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