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

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_09C3E6B613E5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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
Author(s)
Panneman D.M., Hitti-Malin R.J., Holtes L.K., de Bruijn S.E., Reurink J., Boonen EGM, Khan M.I., Ali M., 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 C.F., Karali M., Kjellström U., Koenekoop R., de Koning B., Leroy B.P., McKibbin M., Meunier I., Nikopoulos K., Nishiguchi K.M., Poulter J.A., Rivolta C., Rodríguez de la Rúa E., Saunders P., Simonelli F., Tatour Y., Testa F., Thiadens AAHJ, Toomes C., Tracewska A.M., Tran H.V., Ushida H., Vaclavik V., Verhoeven VJM, van de Vorst M., Gilissen C., Hoischen A., Cremers FPM, Roosing S., Tran H.V., Vaclavik V.
ISSN
2296-634X (Print)
ISSN-L
2296-634X
Publication state
Published
Issued date
2023
Peer-reviewed
Oui
Volume
11
Pages
1112270
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
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
cost-effective, high-throughput, inherited retinal diseases, smMIPs, targeted gene sequencing
Pubmed
Web of science
Open Access
Yes
Create date
13/03/2023 17:43
Last modification date
13/10/2023 7:08
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