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

Daan M. Panneman; Rebekkah J. Hitti-Malin; 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 Nikopoulos; Koji M. Nishiguchi; James A. Poulter; Carlo Rivolta; Enrique Rodríguez de la Rúa; Patrick Saunders; Francesca Simonelli; Yasmin Tatour; Francesco Testa; Alberta A.H.J. Thiadens; Carmel Toomes; Anna M. Tracewska; Hoai Viet Tran; Hiroaki Ushida; Veronika Vaclavik; Virginie J.M. Verhoeven; Maartje van de Vorst; Christian Gilissen; Alexander Hoischen; Frans P.M. Cremers; Susanne Roosing

doi:10.3389/fcell.2023.1112270

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

Daan M. Panneman^*, Rebekkah J. Hitti-Malin, 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. InglehearnMarianthi Karali, Ulrika Kjellström, Robert Koenekoop, Bart de Koning, Bart P. Leroy, Martin McKibbin, Isabelle Meunier, Konstantinos Nikopoulos, Koji M. Nishiguchi, James A. Poulter, Carlo Rivolta, Enrique Rodríguez de la Rúa, Patrick Saunders, Francesca Simonelli, Yasmin Tatour, Francesco Testa, Alberta A.H.J. Thiadens, Carmel Toomes, Anna M. Tracewska, Hoai Viet Tran, Hiroaki Ushida, Veronika Vaclavik, Virginie J.M. Verhoeven, Maartje van de Vorst, Christian Gilissen, Alexander Hoischen, Frans P.M. Cremers, Susanne Roosing

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	1112270
Journal	Frontiers in Cell and Developmental Biology
Volume	11
DOIs	https://doi.org/10.3389/fcell.2023.1112270
Publication status	Published - 3 Feb 2023

Bibliographical note

Publisher Copyright:
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.

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Panneman, D. M., Hitti-Malin, R. J., Holtes, L. K., de Bruijn, S. E., Reurink, J., Boonen, E. G. M., Khan, M. I., Ali, M., Andréasson, S., De Baere, E., Banfi, S., Bauwens, M., Ben-Yosef, T., Bocquet, B., De Bruyne, M., Cerda, B. D. L., Coppieters, F., Farinelli, P., Guignard, T., ... Roosing, S. (2023). Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis. Frontiers in Cell and Developmental Biology, 11, Article 1112270. https://doi.org/10.3389/fcell.2023.1112270

@article{f7afaf6c93cb4b69a7c433102a47fe30,

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.",

author = "Panneman, {Daan M.} and Hitti-Malin, {Rebekkah J.} and Holtes, {Lara K.} and {de Bruijn}, {Suzanne E.} and Janine Reurink and Boonen, {Erica G.M.} and Khan, {Muhammad Imran} and Manir Ali and Sten Andr{\'e}asson and {De Baere}, Elfride and Sandro Banfi and Miriam Bauwens and Tamar Ben-Yosef and B{\'e}atrice Bocquet and {De Bruyne}, Marieke and Cerda, {Berta de la} and Frauke Coppieters and Pietro Farinelli and Thomas Guignard and Inglehearn, {Chris F.} and Marianthi Karali and Ulrika Kjellstr{\"o}m and Robert Koenekoop and {de Koning}, Bart and Leroy, {Bart P.} and Martin McKibbin and Isabelle Meunier and Konstantinos Nikopoulos and Nishiguchi, {Koji M.} and Poulter, {James A.} and Carlo Rivolta and {Rodr{\'i}guez de la R{\'u}a}, Enrique and Patrick Saunders and Francesca Simonelli and Yasmin Tatour and Francesco Testa and Thiadens, {Alberta A.H.J.} and Carmel Toomes and Tracewska, {Anna M.} and Tran, {Hoai Viet} and Hiroaki Ushida and Veronika Vaclavik and Verhoeven, {Virginie J.M.} and {van de Vorst}, Maartje and Christian Gilissen and Alexander Hoischen and Cremers, {Frans P.M.} and Susanne Roosing",

note = "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",

}

Panneman, DM, Hitti-Malin, RJ, Holtes, LK, de Bruijn, SE, Reurink, J, Boonen, EGM, Khan, MI, Ali, M, Andréasson, S, De Baere, E, Banfi, S, Bauwens, M, Ben-Yosef, T, Bocquet, B, De Bruyne, M, Cerda, BDL, Coppieters, F, Farinelli, P, Guignard, T, Inglehearn, CF, 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, Tracewska, AM, Tran, HV, Ushida, H, Vaclavik, V, Verhoeven, VJM, van de Vorst, M, Gilissen, C, Hoischen, A, Cremers, FPM & Roosing, S 2023, 'Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis', Frontiers in Cell and Developmental Biology, vol. 11, 1112270. https://doi.org/10.3389/fcell.2023.1112270

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 - Publisher Copyright: 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.

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U2 - 10.3389/fcell.2023.1112270

DO - 10.3389/fcell.2023.1112270

M3 - Article

C2 - 36819107

AN - SCOPUS:85147341924

SN - 2296-634X

VL - 11

JO - Frontiers in Cell and Developmental Biology

JF - Frontiers in Cell and Developmental Biology

M1 - 1112270

ER -

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

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