alexa De novo mutations in epileptic encephalopathies.
Neurology

Neurology

Autism-Open Access

Author(s): EpiK Consortium Epilepsy, Allen AS, Berkovic SF, Cossette P, Delanty N,

Abstract Share this page

Abstract Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.
This article was published in Nature and referenced in Autism-Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • Neurology and Neurological Disorders
    July 17-18, 2017 Chicago, USA
  • International Conference on Social Sciences & Interdisciplinary Studies
    August 07-17 London, UK
  • 3rd International Conference on Autism
    Aug 21-22, 2017 Los Angeles, USA
  • 3rd International Conference on Epilepsy and Treatment
    September 01-17 Brussels, Belgium

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords