Clinical exome sequencing for inherited retinal degenerations at a tertiary care center
Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a r...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174483/ https://www.ncbi.nlm.nih.gov/pubmed/35672425 http://dx.doi.org/10.1038/s41598-022-13026-2 |
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author | Ganapathi, Mythily Thomas-Wilson, Amanda Buchovecky, Christie Dharmadhikari, Avinash Barua, Subit Lee, Winston Ruan, Merry Z. C. Soucy, Megan Ragi, Sara Tanaka, Joy Clark, Lorraine N. Naini, Ali B. Liao, Jun Mansukhani, Mahesh Tsang, Stephen Jobanputra, Vaidehi |
author_facet | Ganapathi, Mythily Thomas-Wilson, Amanda Buchovecky, Christie Dharmadhikari, Avinash Barua, Subit Lee, Winston Ruan, Merry Z. C. Soucy, Megan Ragi, Sara Tanaka, Joy Clark, Lorraine N. Naini, Ali B. Liao, Jun Mansukhani, Mahesh Tsang, Stephen Jobanputra, Vaidehi |
author_sort | Ganapathi, Mythily |
collection | PubMed |
description | Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders. |
format | Online Article Text |
id | pubmed-9174483 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91744832022-06-09 Clinical exome sequencing for inherited retinal degenerations at a tertiary care center Ganapathi, Mythily Thomas-Wilson, Amanda Buchovecky, Christie Dharmadhikari, Avinash Barua, Subit Lee, Winston Ruan, Merry Z. C. Soucy, Megan Ragi, Sara Tanaka, Joy Clark, Lorraine N. Naini, Ali B. Liao, Jun Mansukhani, Mahesh Tsang, Stephen Jobanputra, Vaidehi Sci Rep Article Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders. Nature Publishing Group UK 2022-06-07 /pmc/articles/PMC9174483/ /pubmed/35672425 http://dx.doi.org/10.1038/s41598-022-13026-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ganapathi, Mythily Thomas-Wilson, Amanda Buchovecky, Christie Dharmadhikari, Avinash Barua, Subit Lee, Winston Ruan, Merry Z. C. Soucy, Megan Ragi, Sara Tanaka, Joy Clark, Lorraine N. Naini, Ali B. Liao, Jun Mansukhani, Mahesh Tsang, Stephen Jobanputra, Vaidehi Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title | Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title_full | Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title_fullStr | Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title_full_unstemmed | Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title_short | Clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
title_sort | clinical exome sequencing for inherited retinal degenerations at a tertiary care center |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174483/ https://www.ncbi.nlm.nih.gov/pubmed/35672425 http://dx.doi.org/10.1038/s41598-022-13026-2 |
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