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Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases

Inherited retinal diseases (IRDs) are a diverse set of visual disorders that collectively represent a major cause of early-onset blindness. With the reduction in sequencing costs in recent years, whole-genome sequencing (WGS) is being used more frequently, particularly when targeted gene panels and...

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Autores principales: Hussain, Hafiz Muhammad Jafar, Wang, Meng, Huang, Austin, Schmidt, Ryan, Qian, Xinye, Yang, Paul, Marra, Molly, Li, Yumei, Pennesi, Mark E., Chen, Rui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956865/
https://www.ncbi.nlm.nih.gov/pubmed/36833373
http://dx.doi.org/10.3390/genes14020447
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author Hussain, Hafiz Muhammad Jafar
Wang, Meng
Huang, Austin
Schmidt, Ryan
Qian, Xinye
Yang, Paul
Marra, Molly
Li, Yumei
Pennesi, Mark E.
Chen, Rui
author_facet Hussain, Hafiz Muhammad Jafar
Wang, Meng
Huang, Austin
Schmidt, Ryan
Qian, Xinye
Yang, Paul
Marra, Molly
Li, Yumei
Pennesi, Mark E.
Chen, Rui
author_sort Hussain, Hafiz Muhammad Jafar
collection PubMed
description Inherited retinal diseases (IRDs) are a diverse set of visual disorders that collectively represent a major cause of early-onset blindness. With the reduction in sequencing costs in recent years, whole-genome sequencing (WGS) is being used more frequently, particularly when targeted gene panels and whole-exome sequencing (WES) fail to detect pathogenic mutations in patients. In this study, we performed mutation screens using WGS for a cohort of 311 IRD patients whose mutations were undetermined. A total of nine putative pathogenic mutations in six IRD patients were identified, including six novel mutations. Among them, four were deep intronic mutations that affected mRNA splicing, while the other five affected protein-coding sequences. Our results suggested that the rate of resolution of unsolved cases via targeted gene panels and WES can be further enhanced with WGS; however, the overall improvement may be limited.
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spelling pubmed-99568652023-02-25 Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases Hussain, Hafiz Muhammad Jafar Wang, Meng Huang, Austin Schmidt, Ryan Qian, Xinye Yang, Paul Marra, Molly Li, Yumei Pennesi, Mark E. Chen, Rui Genes (Basel) Article Inherited retinal diseases (IRDs) are a diverse set of visual disorders that collectively represent a major cause of early-onset blindness. With the reduction in sequencing costs in recent years, whole-genome sequencing (WGS) is being used more frequently, particularly when targeted gene panels and whole-exome sequencing (WES) fail to detect pathogenic mutations in patients. In this study, we performed mutation screens using WGS for a cohort of 311 IRD patients whose mutations were undetermined. A total of nine putative pathogenic mutations in six IRD patients were identified, including six novel mutations. Among them, four were deep intronic mutations that affected mRNA splicing, while the other five affected protein-coding sequences. Our results suggested that the rate of resolution of unsolved cases via targeted gene panels and WES can be further enhanced with WGS; however, the overall improvement may be limited. MDPI 2023-02-09 /pmc/articles/PMC9956865/ /pubmed/36833373 http://dx.doi.org/10.3390/genes14020447 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hussain, Hafiz Muhammad Jafar
Wang, Meng
Huang, Austin
Schmidt, Ryan
Qian, Xinye
Yang, Paul
Marra, Molly
Li, Yumei
Pennesi, Mark E.
Chen, Rui
Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title_full Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title_fullStr Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title_full_unstemmed Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title_short Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases
title_sort novel pathogenic mutations identified from whole-genome sequencing in unsolved cases of patients affected with inherited retinal diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9956865/
https://www.ncbi.nlm.nih.gov/pubmed/36833373
http://dx.doi.org/10.3390/genes14020447
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