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

Panneman, Daan M. ; Hitti-Malin, Rebekkah J. ; Holtes, Lara K. ; de Bruijn, Suzanne E. ; Reurink, Janine ; Boonen, Erica G.M. ; Khan, Muhammad Imran ; Ali, Manir ; Andréasson, Sten LU and De Baere, Elfride , et al. (2023) In Frontiers in cell and developmental biology 11.
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... (More)

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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publication status
published
subject
keywords
cost-effective, high-throughput, inherited retinal diseases, smMIPs, targeted gene sequencing
in
Frontiers in cell and developmental biology
volume
11
article number
1112270
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85147341924
  • pmid:36819107
ISSN
2296-634X
DOI
10.3389/fcell.2023.1112270
language
English
LU publication?
yes
id
1e2c7301-6eec-43e1-8240-1d6d7c81d55c
date added to LUP
2024-01-12 13:06:35
date last changed
2024-04-13 07:15:31
@article{1e2c7301-6eec-43e1-8240-1d6d7c81d55c,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Panneman, Daan M. and Hitti-Malin, Rebekkah J. and Holtes, Lara K. and de Bruijn, Suzanne E. and Reurink, Janine and Boonen, Erica G.M. and Khan, Muhammad Imran and Ali, Manir and Andréasson, Sten and De Baere, Elfride and Banfi, Sandro and Bauwens, Miriam and Ben-Yosef, Tamar and Bocquet, Béatrice and De Bruyne, Marieke and Cerda, Berta de la and Coppieters, Frauke and Farinelli, Pietro and Guignard, Thomas and Inglehearn, Chris F. and Karali, Marianthi and Kjellström, Ulrika and Koenekoop, Robert and de Koning, Bart and Leroy, Bart P. and McKibbin, Martin and Meunier, Isabelle and Nikopoulos, Konstantinos and Nishiguchi, Koji M. and Poulter, James A. and Rivolta, Carlo and Rodríguez de la Rúa, Enrique and Saunders, Patrick and Simonelli, Francesca and Tatour, Yasmin and Testa, Francesco and Thiadens, Alberta A.H.J. and Toomes, Carmel and Tracewska, Anna M. and Tran, Hoai Viet and Ushida, Hiroaki and Vaclavik, Veronika and Verhoeven, Virginie J.M. and van de Vorst, Maartje and Gilissen, Christian and Hoischen, Alexander and Cremers, Frans P.M. and Roosing, Susanne}},
  issn         = {{2296-634X}},
  keywords     = {{cost-effective; high-throughput; inherited retinal diseases; smMIPs; targeted gene sequencing}},
  language     = {{eng}},
  month        = {{02}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in cell and developmental biology}},
  title        = {{Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis}},
  url          = {{http://dx.doi.org/10.3389/fcell.2023.1112270}},
  doi          = {{10.3389/fcell.2023.1112270}},
  volume       = {{11}},
  year         = {{2023}},
}