TY - JOUR
T1 - Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
AU - Panneman, Daan M.
AU - Hitti-Malin, Rebekkah J.
AU - Holtes, Lara K.
AU - de Bruijn, Suzanne E.
AU - Reurink, Janine
AU - Boonen, Erica G.M.
AU - Khan, Muhammad Imran
AU - Ali, Manir
AU - Andréasson, Sten
AU - De Baere, Elfride
AU - Banfi, Sandro
AU - Bauwens, Miriam
AU - Ben-Yosef, Tamar
AU - Bocquet, Béatrice
AU - De Bruyne, Marieke
AU - Cerda, Berta de la
AU - Coppieters, Frauke
AU - Farinelli, Pietro
AU - Guignard, Thomas
AU - Inglehearn, Chris F.
AU - Karali, Marianthi
AU - Kjellström, Ulrika
AU - Koenekoop, Robert
AU - de Koning, Bart
AU - Leroy, Bart P.
AU - McKibbin, Martin
AU - Meunier, Isabelle
AU - Nikopoulos, Konstantinos
AU - Nishiguchi, Koji M.
AU - Poulter, James A.
AU - Rivolta, Carlo
AU - Rodríguez de la Rúa, Enrique
AU - Saunders, Patrick
AU - Simonelli, Francesca
AU - Tatour, Yasmin
AU - Testa, Francesco
AU - Thiadens, Alberta A.H.J.
AU - Toomes, Carmel
AU - Tracewska, Anna M.
AU - Tran, Hoai Viet
AU - Ushida, Hiroaki
AU - Vaclavik, Veronika
AU - Verhoeven, Virginie J.M.
AU - van de Vorst, Maartje
AU - Gilissen, Christian
AU - Hoischen, Alexander
AU - Cremers, Frans P.M.
AU - Roosing, Susanne
N1 - Copyright © 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.
PY - 2023/2/3
Y1 - 2023/2/3
N2 - 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.
AB - 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.
KW - cost-effective
KW - high-throughput
KW - inherited retinal diseases
KW - smMIPs
KW - targeted gene sequencing
UR - http://www.scopus.com/inward/record.url?scp=85147341924&partnerID=8YFLogxK
U2 - 10.3389/fcell.2023.1112270
DO - 10.3389/fcell.2023.1112270
M3 - مقالة
C2 - 36819107
SN - 2296-634X
VL - 11
SP - 1112270
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 1112270
ER -