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Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center
Exome sequencing (ES) became clinically available in 2011 and promised an agnostic, unbiased next-generation sequencing (NGS) platform for patients with symptoms believed to have a genetic etiology. The diagnostic yield of ES has been estimated to be between 25–40% and may be higher in specific clin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355124/ https://www.ncbi.nlm.nih.gov/pubmed/35937981 http://dx.doi.org/10.3389/fgene.2022.887698 |
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author | Baker, Elizabeth K. Ulm, Elizabeth A. Belonis, Alyce Brightman, Diana S. Hallinan, Barbara E. Leslie, Nancy D. Miethke, Alexander G. Vawter-Lee, Marissa Wu, Yaning Pena, Loren D. M. |
author_facet | Baker, Elizabeth K. Ulm, Elizabeth A. Belonis, Alyce Brightman, Diana S. Hallinan, Barbara E. Leslie, Nancy D. Miethke, Alexander G. Vawter-Lee, Marissa Wu, Yaning Pena, Loren D. M. |
author_sort | Baker, Elizabeth K. |
collection | PubMed |
description | Exome sequencing (ES) became clinically available in 2011 and promised an agnostic, unbiased next-generation sequencing (NGS) platform for patients with symptoms believed to have a genetic etiology. The diagnostic yield of ES has been estimated to be between 25–40% and may be higher in specific clinical scenarios. Those who remain undiagnosed may have no molecular findings of interest on ES, variants of uncertain significance in genes that are linked to human disease, or variants of uncertain significance in candidate genes that are not definitively tied to human disease. Recent evidence suggests that a post-exome evaluation consisting of clinical re-phenotyping, functional studies of candidate variants in known genes, and variant reevaluation can lead to a diagnosis in 5–15% of additional cases. In this brief research study, we present our experience on post-exome evaluations in a cohort of patients who are believed to have a genetic etiology for their symptoms. We have reached a full or partial diagnosis in approximately 18% (6/33) of cases that have completed evaluations to date. We accomplished this by utilizing NGS-based methods that are available on a clinical basis. A sample of these cases highlights the utility of ES reanalysis with updated phenotyping allowing for the discovery of new genes, re-adjudication of known variants, incorporating updated phenotypic information, utilizing functional testing such as targeted RNA sequencing, and deploying other NGS-based testing methods such as gene panels and genome sequencing to reach a diagnosis. |
format | Online Article Text |
id | pubmed-9355124 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93551242022-08-06 Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center Baker, Elizabeth K. Ulm, Elizabeth A. Belonis, Alyce Brightman, Diana S. Hallinan, Barbara E. Leslie, Nancy D. Miethke, Alexander G. Vawter-Lee, Marissa Wu, Yaning Pena, Loren D. M. Front Genet Genetics Exome sequencing (ES) became clinically available in 2011 and promised an agnostic, unbiased next-generation sequencing (NGS) platform for patients with symptoms believed to have a genetic etiology. The diagnostic yield of ES has been estimated to be between 25–40% and may be higher in specific clinical scenarios. Those who remain undiagnosed may have no molecular findings of interest on ES, variants of uncertain significance in genes that are linked to human disease, or variants of uncertain significance in candidate genes that are not definitively tied to human disease. Recent evidence suggests that a post-exome evaluation consisting of clinical re-phenotyping, functional studies of candidate variants in known genes, and variant reevaluation can lead to a diagnosis in 5–15% of additional cases. In this brief research study, we present our experience on post-exome evaluations in a cohort of patients who are believed to have a genetic etiology for their symptoms. We have reached a full or partial diagnosis in approximately 18% (6/33) of cases that have completed evaluations to date. We accomplished this by utilizing NGS-based methods that are available on a clinical basis. A sample of these cases highlights the utility of ES reanalysis with updated phenotyping allowing for the discovery of new genes, re-adjudication of known variants, incorporating updated phenotypic information, utilizing functional testing such as targeted RNA sequencing, and deploying other NGS-based testing methods such as gene panels and genome sequencing to reach a diagnosis. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9355124/ /pubmed/35937981 http://dx.doi.org/10.3389/fgene.2022.887698 Text en Copyright © 2022 Baker, Ulm, Belonis, Brightman, Hallinan, Leslie, Miethke, Vawter-Lee, Wu and Pena. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Baker, Elizabeth K. Ulm, Elizabeth A. Belonis, Alyce Brightman, Diana S. Hallinan, Barbara E. Leslie, Nancy D. Miethke, Alexander G. Vawter-Lee, Marissa Wu, Yaning Pena, Loren D. M. Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title | Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title_full | Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title_fullStr | Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title_full_unstemmed | Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title_short | Clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
title_sort | clinically available testing options resulting in diagnosis in post-exome clinic at one medical center |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355124/ https://www.ncbi.nlm.nih.gov/pubmed/35937981 http://dx.doi.org/10.3389/fgene.2022.887698 |
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