Journal article
The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield
Epilepsia (Copenhagen), Vol.60(5), pp.797-806
05/2019
DOI: 10.1111/epi.14698
PMCID: PMC6519344
PMID: 30951195
Abstract
Summary
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.
Details
- Title: Subtitle
- The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield
- Creators
- Colleen CampbellMichael CilibertoCharuta JoshiDavid B GoldsteinErin L HeinzenMichelle E ErnstBrandon L LaughlinDaniel H LowensteinLaura LubbersRandall StewartVicky WhittemoreKaitlin AngioneCarl W BazilLouise BierJudith BluvsteinElise BrimbleGianpiero CavalleriMaria Roberta CilioChelsea ChambersHyunmi ChoiSusannah CornesNorman DelantyScott DemarestOrrin DevinskyDennis DlugosHolly DubbsPatricia DuganMelissa GibbonsHoward P GoodkinIngo HelbigLaura JansenKaleas JohnsonNatalie C LippaEric MarshAlejandro MartinezJohn MillichapMaureen S MulhernAdam NumisKristen ParkTommaso PippucciAnnapurna PoduriBrenda PorterBrigid ReganTristan T SandsIngrid E SchefferJohn M SchreiberBeth SheidleyNilika SinghalLacey SmithJoseph SullivanAlan TaylorPatricia ToleteTahseen M AfganiVimla AggarwalRosemary BurgessTracy Dixon‐SalazarParisa HematiJulie MilderSlavé PetrovskiAnya Revah‐PolitiNicholas StongEpilepsy Genetics Initiative (EGI) Steering Committee
- Resource Type
- Journal article
- Publication Details
- Epilepsia (Copenhagen), Vol.60(5), pp.797-806
- DOI
- 10.1111/epi.14698
- PMID
- 30951195
- PMCID
- PMC6519344
- NLM abbreviation
- Epilepsia
- ISSN
- 0013-9580
- eISSN
- 1528-1167
- Number of pages
- 10
- Grant note
- Citizens United for Research in Epilepsy (339143) National Institute for Neurological Disease and Stroke (U01‐NS077303‐04S1) The John and Barbara Vogelstein Foundation
- Language
- English
- Date published
- 05/2019
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Cardiovascular Medicine; Neurology (Pediatrics); Internal Medicine
- Record Identifier
- 9984094626502771
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