Frontiers in Cell and Developmental Biology (Feb 2023)
Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- Daan M. Panneman,
- Daan M. Panneman,
- Rebekkah J. Hitti-Malin,
- Rebekkah J. Hitti-Malin,
- Lara K. Holtes,
- Suzanne E. de Bruijn,
- Suzanne E. de Bruijn,
- Janine Reurink,
- Janine Reurink,
- Erica G. M. Boonen,
- Muhammad Imran Khan,
- Manir Ali,
- Sten Andréasson,
- Elfride De Baere,
- Elfride De Baere,
- Sandro Banfi,
- Sandro Banfi,
- Miriam Bauwens,
- Miriam Bauwens,
- Tamar Ben-Yosef,
- Béatrice Bocquet,
- Béatrice Bocquet,
- Marieke De Bruyne,
- Marieke De Bruyne,
- Berta de la Cerda,
- Frauke Coppieters,
- Frauke Coppieters,
- Frauke Coppieters,
- Pietro Farinelli,
- Thomas Guignard,
- Chris F. Inglehearn,
- Marianthi Karali,
- Marianthi Karali,
- Ulrika Kjellström,
- Robert Koenekoop,
- Robert Koenekoop,
- Bart de Koning,
- Bart P. Leroy,
- Bart P. Leroy,
- Bart P. Leroy,
- Bart P. Leroy,
- Martin McKibbin,
- Martin McKibbin,
- Isabelle Meunier,
- Isabelle Meunier,
- Konstantinos Nikopoulos,
- Koji M. Nishiguchi,
- James A. Poulter,
- Carlo Rivolta,
- Carlo Rivolta,
- 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,
- Virginie J. M. Verhoeven,
- Maartje van de Vorst,
- Christian Gilissen,
- Christian Gilissen,
- Alexander Hoischen,
- Alexander Hoischen,
- Alexander Hoischen,
- Frans P. M. Cremers,
- Frans P. M. Cremers,
- Susanne Roosing,
- Susanne Roosing
Affiliations
- Daan M. Panneman
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Daan M. Panneman
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- Rebekkah J. Hitti-Malin
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Rebekkah J. Hitti-Malin
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- Lara K. Holtes
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Suzanne E. de Bruijn
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Suzanne E. de Bruijn
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- Janine Reurink
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Janine Reurink
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- Erica G. M. Boonen
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Muhammad Imran Khan
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Manir Ali
- Division of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom
- Sten Andréasson
- Department of Ophthalmology and Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
- Elfride De Baere
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
- Elfride De Baere
- Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
- Sandro Banfi
- Telethon Institute of Genetics and Medicine, Pozzuoli, Italy
- Sandro Banfi
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Miriam Bauwens
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
- Miriam Bauwens
- Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
- Tamar Ben-Yosef
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Béatrice Bocquet
- 0National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, Montpellier, France
- Béatrice Bocquet
- 1Institute for Neurosciences of Montpellier (INM), L’Institut National de la Santé et de la Recherche Médicale, University of Montpellier, L’Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- Marieke De Bruyne
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
- Marieke De Bruyne
- Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
- Berta de la Cerda
- 2Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, Spain
- Frauke Coppieters
- Department of Biomolecular Medicine, Ghent University, Ghent, Belgium
- Frauke Coppieters
- Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
- Frauke Coppieters
- 3Department of Pharmaceutics, Ghent University, Ghent, Belgium
- Pietro Farinelli
- 4Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne, Switzerland
- Thomas Guignard
- 5Chromosomal Genetics Unit, University Hospital of Montpellier, Montpellier, France
- Chris F. Inglehearn
- Division of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom
- Marianthi Karali
- Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy
- Marianthi Karali
- 6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
- Ulrika Kjellström
- Department of Ophthalmology and Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden
- Robert Koenekoop
- 7McGill University Health Center (MUHC) Research Institute, Montreal, QC, Canada
- Robert Koenekoop
- 8Departments of Paediatric Surgery, Human Genetics, and Adult Ophthalmology, McGill University Health Center, Montreal, QC, Canada
- Bart de Koning
- 9Department of Clinical Genetics, Maastricht University Medical Center+ (MUMC+), Maastricht, Netherlands
- Bart P. Leroy
- 0Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium
- Bart P. Leroy
- 1Department of Head & Skin, Ghent University, Ghent, Belgium
- Bart P. Leroy
- 2Division of Ophthalmology & Center for Cellular & Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States
- Bart P. Leroy
- 3Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium
- Martin McKibbin
- Division of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom
- Martin McKibbin
- 4Department of Ophthalmology, St. James’s University Hospital, Leeds, United Kingdom
- Isabelle Meunier
- 0National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, Montpellier, France
- Isabelle Meunier
- 1Institute for Neurosciences of Montpellier (INM), L’Institut National de la Santé et de la Recherche Médicale, University of Montpellier, L’Institut National de la Santé et de la Recherche Médicale, Montpellier, France
- Konstantinos Nikopoulos
- 5Laboratory of molecular diagnostics, UNILABS SA, Lausanne, Switzerland
- Koji M. Nishiguchi
- 6Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- James A. Poulter
- Division of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom
- Carlo Rivolta
- 7Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland
- Carlo Rivolta
- 8Department of Ophthalmology, University of Basel, Basel, Switzerland
- Carlo Rivolta
- 9Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom
- Enrique Rodríguez de la Rúa
- 0Department of Ophthalmology, Retics Patologia Ocular, OFTARED, Instituto de Salud Carlos III, University Hospital Virgen Macarena, Madrid, Spain
- Patrick Saunders
- 1Molecular Loop Biosciences Inc., Woburn, MA, United States
- Francesca Simonelli
- 6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
- Yasmin Tatour
- Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
- Francesco Testa
- 6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
- Alberta A. H. J. Thiadens
- 2Department of Ophthalmology, Erasmus, Rotterdam, Netherlands
- Carmel Toomes
- Division of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom
- Anna M. Tracewska
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Hoai Viet Tran
- 3Oculogenetic Unit, University Eye Hospital Jules Gonin, Geneva, Switzerland
- Hiroaki Ushida
- 6Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Veronika Vaclavik
- 3Oculogenetic Unit, University Eye Hospital Jules Gonin, Geneva, Switzerland
- Virginie J. M. Verhoeven
- 2Department of Ophthalmology, Erasmus, Rotterdam, Netherlands
- Virginie J. M. Verhoeven
- 4Department of Clinical Genetics, Erasmus, Rotterdam, Netherlands
- Maartje van de Vorst
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Christian Gilissen
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Christian Gilissen
- 5Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Alexander Hoischen
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Alexander Hoischen
- 5Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
- Alexander Hoischen
- 6Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands
- Frans P. M. Cremers
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Frans P. M. Cremers
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- Susanne Roosing
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands
- Susanne Roosing
- Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands
- DOI
- https://doi.org/10.3389/fcell.2023.1112270
- Journal volume & issue
-
Vol. 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 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
