Columbia University Irving Medical Center, New York, New York.
Epilepsia. 2019 May;60(5):797-806. doi: 10.1111/epi.14698. Epub 2019 Apr 5.
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.
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.
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.
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.
癫痫遗传学倡议（EGI）成立于 2014 年，旨在创建一个集中管理的临床生成外显子组序列数据库。EGI 进行系统的基于研究的重新分析，以确定在初始测序时不可能的新分子诊断，并帮助发现新基因。本文报告了成立 3 年后该方法的效果。
纳入了 166 名接受诊断性全外显子组测序（WES）的癫痫患者，包括 139 名未获得遗传诊断的患者。将序列数据传输到 EGI，并定期进行基于研究的重新评估。
在初始诊断分析后，由于更新注释或发现新的癫痫基因，做出了 8 个新诊断。在另外 5 例中，我们提供了新的证据来支持或反驳实验室报告的变异致病性的可能性。通过对研究和临床生成的 WES 的双重询问发现了一个新的癫痫基因。
EGI 的诊断率为 5.8%，代表诊断产量有了相当大的提高，证明了定期重新分析全外显子数据的价值。该倡议对基因发现的贡献强调了数据共享的重要性和合作企业的价值。
