Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
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 associat...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1112270/full |
| _version_ | 1811173218218672128 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Daan M. Panneman |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T17:43:16Z |
| format | Article |
| id | doaj.art-70773f087bee4d9ea754539e4fee1ac1 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T17:43:16Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-70773f087bee4d9ea754539e4fee1ac12023-02-03T06:21:29ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-02-011110.3389/fcell.2023.11122701112270Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosisDaan M. Panneman0Daan M. Panneman1Rebekkah J. Hitti-Malin2Rebekkah J. Hitti-Malin3Lara K. Holtes4Suzanne E. de Bruijn5Suzanne E. de Bruijn6Janine Reurink7Janine Reurink8Erica G. M. Boonen9Muhammad Imran Khan10Manir Ali11Sten Andréasson12Elfride De Baere13Elfride De Baere14Sandro Banfi15Sandro Banfi16Miriam Bauwens17Miriam Bauwens18Tamar Ben-Yosef19Béatrice Bocquet20Béatrice Bocquet21Marieke De Bruyne22Marieke De Bruyne23Berta de la Cerda24Frauke Coppieters25Frauke Coppieters26Frauke Coppieters27Pietro Farinelli28Thomas Guignard29Chris F. Inglehearn30Marianthi Karali31Marianthi Karali32Ulrika Kjellström33Robert Koenekoop34Robert Koenekoop35Bart de Koning36Bart P. Leroy37Bart P. Leroy38Bart P. Leroy39Bart P. Leroy40Martin McKibbin41Martin McKibbin42Isabelle Meunier43Isabelle Meunier44Konstantinos Nikopoulos45Koji M. Nishiguchi46James A. Poulter47Carlo Rivolta48Carlo Rivolta49Carlo Rivolta50Enrique Rodríguez de la Rúa51Patrick Saunders52Francesca Simonelli53Yasmin Tatour54Francesco Testa55Alberta A. H. J. Thiadens56Carmel Toomes57Anna M. Tracewska58Hoai Viet Tran59Hiroaki Ushida60Veronika Vaclavik61Virginie J. M. Verhoeven62Virginie J. M. Verhoeven63Maartje van de Vorst64Christian Gilissen65Christian Gilissen66Alexander Hoischen67Alexander Hoischen68Alexander Hoischen69Frans P. M. Cremers70Frans P. M. Cremers71Susanne Roosing72Susanne Roosing73Department of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDivision of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United KingdomDepartment of Ophthalmology and Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, SwedenDepartment of Biomolecular Medicine, Ghent University, Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Ghent, BelgiumTelethon Institute of Genetics and Medicine, Pozzuoli, ItalyDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, ItalyDepartment of Biomolecular Medicine, Ghent University, Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Ghent, BelgiumRappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel0National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, Montpellier, France1Institute 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, FranceDepartment of Biomolecular Medicine, Ghent University, Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium2Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER), Seville, SpainDepartment of Biomolecular Medicine, Ghent University, Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Ghent, Belgium3Department of Pharmaceutics, Ghent University, Ghent, Belgium4Department of Computational Biology, Unit of Medical Genetics, University of Lausanne, Lausanne, Switzerland5Chromosomal Genetics Unit, University Hospital of Montpellier, Montpellier, FranceDivision of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United KingdomDepartment of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, ItalyDepartment of Ophthalmology and Clinical Sciences Lund, Lund University, Skane University Hospital, Lund, Sweden7McGill University Health Center (MUHC) Research Institute, Montreal, QC, Canada8Departments of Paediatric Surgery, Human Genetics, and Adult Ophthalmology, McGill University Health Center, Montreal, QC, Canada9Department of Clinical Genetics, Maastricht University Medical Center+ (MUMC+), Maastricht, Netherlands0Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium1Department of Head & Skin, Ghent University, Ghent, Belgium2Division of Ophthalmology & Center for Cellular & Molecular Therapeutics, Children’s Hospital of Philadelphia, Philadelphia, PA, United States3Center for Medical Genetics, Ghent University Hospital, Ghent, BelgiumDivision of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom4Department of Ophthalmology, St. James’s University Hospital, Leeds, United Kingdom0National Reference Centre for Inherited Sensory Diseases, University of Montpellier, Montpellier University Hospital, Sensgene Care Network, ERN-EYE Network, Montpellier, France1Institute 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, France5Laboratory of molecular diagnostics, UNILABS SA, Lausanne, Switzerland6Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, JapanDivision of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United Kingdom7Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland8Department of Ophthalmology, University of Basel, Basel, Switzerland9Department of Genetics and Genome Biology, University of Leicester, Leicester, United Kingdom0Department of Ophthalmology, Retics Patologia Ocular, OFTARED, Instituto de Salud Carlos III, University Hospital Virgen Macarena, Madrid, Spain1Molecular Loop Biosciences Inc., Woburn, MA, United States6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, ItalyRappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel6Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania Luigi Vanvitelli, Naples, Italy2Department of Ophthalmology, Erasmus, Rotterdam, NetherlandsDivision of Molecular Medicine, Leeds Institute of Medical Research, St. James’s University Hospital, University of Leeds, Leeds, United KingdomDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands3Oculogenetic Unit, University Eye Hospital Jules Gonin, Geneva, Switzerland6Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan3Oculogenetic Unit, University Eye Hospital Jules Gonin, Geneva, Switzerland2Department of Ophthalmology, Erasmus, Rotterdam, Netherlands4Department of Clinical Genetics, Erasmus, Rotterdam, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands5Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, Netherlands5Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands6Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, NetherlandsDonders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, NetherlandsIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fcell.2023.1112270/fullinherited retinal diseasestargeted gene sequencingcost-effectivehigh-throughputsmMIPs |
| spellingShingle | 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 Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis Frontiers in Cell and Developmental Biology inherited retinal diseases targeted gene sequencing cost-effective high-throughput smMIPs |
| title | Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis |
| title_full | Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis |
| title_fullStr | Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis |
| title_full_unstemmed | Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis |
| title_short | Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis |
| title_sort | cost effective sequence analysis of 113 genes in 1 192 probands with retinitis pigmentosa and leber congenital amaurosis |
| topic | inherited retinal diseases targeted gene sequencing cost-effective high-throughput smMIPs |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1112270/full |
| work_keys_str_mv | AT daanmpanneman costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT daanmpanneman costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT rebekkahjhittimalin costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT rebekkahjhittimalin costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT larakholtes costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT suzanneedebruijn costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT suzanneedebruijn costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT janinereurink costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT janinereurink costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT ericagmboonen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT muhammadimrankhan costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT manirali costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT stenandreasson costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT elfridedebaere costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT elfridedebaere costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT sandrobanfi costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT sandrobanfi costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT miriambauwens costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT miriambauwens costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT tamarbenyosef costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT beatricebocquet costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT beatricebocquet costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT mariekedebruyne costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT mariekedebruyne costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bertadelacerda costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT fraukecoppieters costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT fraukecoppieters costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT fraukecoppieters costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT pietrofarinelli costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT thomasguignard costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT chrisfinglehearn costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT marianthikarali costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT marianthikarali costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT ulrikakjellstrom costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT robertkoenekoop costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT robertkoenekoop costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bartdekoning costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bartpleroy costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bartpleroy costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bartpleroy costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT bartpleroy costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT martinmckibbin costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT martinmckibbin costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT isabellemeunier costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT isabellemeunier costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT konstantinosnikopoulos costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT kojimnishiguchi costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT jamesapoulter costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT carlorivolta costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT carlorivolta costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT carlorivolta costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT enriquerodriguezdelarua costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT patricksaunders costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT francescasimonelli costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT yasmintatour costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT francescotesta costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT albertaahjthiadens costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT carmeltoomes costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT annamtracewska costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT hoaiviettran costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT hiroakiushida costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT veronikavaclavik costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT virginiejmverhoeven costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT virginiejmverhoeven costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT maartjevandevorst costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT christiangilissen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT christiangilissen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT alexanderhoischen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT alexanderhoischen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT alexanderhoischen costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT franspmcremers costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT franspmcremers costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT susanneroosing costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis AT susanneroosing costeffectivesequenceanalysisof113genesin1192probandswithretinitispigmentosaandlebercongenitalamaurosis |