University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    ExACtly zero or once A clinically helpful guide to assessing genetic variants in mild epilepsies

    Thumbnail
    Download
    Published version (151.0Kb)

    Citations
    Scopus
    Web of Science
    Altmetric
    18
    19
    Author
    Bennett, CA; Petrovski, S; Oliver, KL; Berkovic, SF
    Date
    2017-08-01
    Source Title
    Neurology Genetics
    Publisher
    LIPPINCOTT WILLIAMS & WILKINS
    University of Melbourne Author/s
    Petrovski, Slave; Bennett, Caitlin; Broderick, Karen; Berkovic, Samuel
    Affiliation
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Bennett, C. A., Petrovski, S., Oliver, K. L. & Berkovic, S. F. (2017). ExACtly zero or once A clinically helpful guide to assessing genetic variants in mild epilepsies. NEUROLOGY-GENETICS, 3 (4), https://doi.org/10.1212/NXG.0000000000000163.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/254820
    DOI
    10.1212/NXG.0000000000000163
    Abstract
    OBJECTIVE: To assist the interpretation of genomic data for common epilepsies, we asked whether variants implicated in mild epilepsies in autosomal dominant families are present in the general population. METHODS: We studied 12 genes for the milder epilepsies and identified published variants with strong segregation support (de novo germline mutation or ≥4 affected family members). These variants were checked in the Exome Aggregation Consortium (ExAC), a database of genetic variation in over 60,000 individuals. We subsequently evaluated variants in these epilepsy genes that lacked strong segregation support. To determine whether the findings in epilepsies were representative of other diseases, we also assessed the presence of variants in other dominant neurologic disorders (e.g., CADASIL). RESULTS: Published epilepsy variants with strong segregation support (n = 65) were absent (n = 61) or present once (n = 4) in ExAC. By contrast, of 46 published epilepsy variants without strong segregation support, 8 occurred recurrently (2-186 times). Similarly, none of the 45 disease-associated variants from other neurologic disorders with strong segregation support occurred more than once in ExAC. Reanalysis using the larger ExAC V2 plus gnomAD reference cohort showed consistent results. CONCLUSIONS: Variants causing autosomal dominant epilepsies are ultra-rare in the general population. Variants observed more than once in ExAC were only found among reports without strong segregation support, suggesting that they may be benign. Clinicians are increasingly faced with the interpretation of genetic variants of unknown significance. These data illustrate that variants present more than once in ExAC are less likely to be pathogenic, reinforcing the valuable clinical role of ExAC.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Medicine and Radiology - Research Publications [2347]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors