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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
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.
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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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