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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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/2/447 |
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| author | Hafiz Muhammad Jafar Hussain Meng Wang Austin Huang Ryan Schmidt Xinye Qian Paul Yang Molly Marra Yumei Li Mark E. Pennesi Rui Chen |
| author_facet | Hafiz Muhammad Jafar Hussain Meng Wang Austin Huang Ryan Schmidt Xinye Qian Paul Yang Molly Marra Yumei Li Mark E. Pennesi Rui Chen |
| author_sort | Hafiz Muhammad Jafar Hussain |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:46:53Z |
| format | Article |
| id | doaj.art-69870df22f1b45fdba9943c69072843b |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:46:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-69870df22f1b45fdba9943c69072843b2023-11-16T20:43:05ZengMDPI AGGenes2073-44252023-02-0114244710.3390/genes14020447Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal DiseasesHafiz Muhammad Jafar Hussain0Meng Wang1Austin Huang2Ryan Schmidt3Xinye Qian4Paul Yang5Molly Marra6Yumei Li7Mark E. Pennesi8Rui Chen9Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USADepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USADepartment of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USADepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USAInherited 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.https://www.mdpi.com/2073-4425/14/2/447inherited retinal diseaseswhole-genome sequencing (WGS)targeted gene panelswhole-exome sequencingdeep intronic mutations |
| spellingShingle | Hafiz Muhammad Jafar Hussain Meng Wang Austin Huang Ryan Schmidt Xinye Qian Paul Yang Molly Marra Yumei Li Mark E. Pennesi Rui Chen Novel Pathogenic Mutations Identified from Whole-Genome Sequencing in Unsolved Cases of Patients Affected with Inherited Retinal Diseases Genes inherited retinal diseases whole-genome sequencing (WGS) targeted gene panels whole-exome sequencing deep intronic mutations |
| 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 | inherited retinal diseases whole-genome sequencing (WGS) targeted gene panels whole-exome sequencing deep intronic mutations |
| url | https://www.mdpi.com/2073-4425/14/2/447 |
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