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The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield
OBJECTIVE: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research‐based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and...
Formato: | Online Artículo Texto |
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Lenguaje: | English |
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John Wiley and Sons Inc.
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519344/ https://www.ncbi.nlm.nih.gov/pubmed/30951195 http://dx.doi.org/10.1111/epi.14698 |
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collection | PubMed |
description | OBJECTIVE: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research‐based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and to aid in novel gene discovery. Herein we report on the efficacy of this approach 3 years after inception. METHODS: One hundred sixty‐six individuals with epilepsy who underwent diagnostic whole exome sequencing (WES) were enrolled, including 139 who had not received a genetic diagnosis. Sequence data were transferred to the EGI and periodically reevaluated on a research basis. RESULTS: Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. In five additional cases, we provided new evidence to support or contradict the likelihood of variant pathogenicity reported by the laboratory. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated WES. SIGNIFICANCE: EGI's diagnosis rate of 5.8% represents a considerable increase in diagnostic yield and demonstrates the value of periodic reinterrogation of whole exome data. The initiative's contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises. |
format | Online Article Text |
id | pubmed-6519344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65193442019-05-23 The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield Epilepsia Full‐length Original Research OBJECTIVE: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI performs systematic research‐based reanalysis to identify new molecular diagnoses that were not possible at the time of initial sequencing and to aid in novel gene discovery. Herein we report on the efficacy of this approach 3 years after inception. METHODS: One hundred sixty‐six individuals with epilepsy who underwent diagnostic whole exome sequencing (WES) were enrolled, including 139 who had not received a genetic diagnosis. Sequence data were transferred to the EGI and periodically reevaluated on a research basis. RESULTS: Eight new diagnoses were made as a result of updated annotations or the discovery of novel epilepsy genes after the initial diagnostic analysis was performed. In five additional cases, we provided new evidence to support or contradict the likelihood of variant pathogenicity reported by the laboratory. One novel epilepsy gene was discovered through dual interrogation of research and clinically generated WES. SIGNIFICANCE: EGI's diagnosis rate of 5.8% represents a considerable increase in diagnostic yield and demonstrates the value of periodic reinterrogation of whole exome data. The initiative's contributions to gene discovery underscore the importance of data sharing and the value of collaborative enterprises. John Wiley and Sons Inc. 2019-04-05 2019-05 /pmc/articles/PMC6519344/ /pubmed/30951195 http://dx.doi.org/10.1111/epi.14698 Text en © 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Full‐length Original Research The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title | The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title_full | The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title_fullStr | The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title_full_unstemmed | The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title_short | The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield |
title_sort | epilepsy genetics initiative: systematic reanalysis of diagnostic exomes increases yield |
topic | Full‐length Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519344/ https://www.ncbi.nlm.nih.gov/pubmed/30951195 http://dx.doi.org/10.1111/epi.14698 |
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