Genomics in the Investigation of Epilepsy (GenIE) Study

• Research type

  Research Study

• Full title

  Can stratification of childhood epilepsy through detailed phenotyping and whole genome sequencing identify novel genetic aetiologies and genetic modifiers of treatment response?

• IRAS ID

  170749

• Contact name

  Sameer Zuberi

• Contact email

  sameer.zuberi@nhs.net

• Sponsor organisation

  NHS Greater Glasgow & Clyde

• Duration of Study in the UK

  4 years, 0 months, 2 days

• Research summary

  Background:
  Epilepsy is the commonest serious neurological disease, affecting 50-60 million people worldwide. Approximately 60% of all epilepsy is primarily genetic in nature. More than 500 different genes have now been identified as important in the causation of epilepsy.
  The recent advance of genetic technology now offers the benefits of genetic diagnosis to many families for whom this had previously not been possible. Benefits of genetic diagnosis include offering an explanation for the epilepsy, counselling for recurrence risk in future offspring, and guidance on prognosis. In some cases genetic diagnosis informs epilepsy treatment choice.
  Epilepsy can be very difficult to treat. For one third of patients with epilepsy the condition is resistant to treatment, or "refractory". A “personalised medicine” approach, where treatment is tailored to the genetic makeup to the individual, may help reduce this proportion of refractory cases, and improve outcomes.

  Aims:
  1. To investigate whether the application of Next Generation Sequencing (NGS) technology, including gene panels, Whole Exome Sequencing (WES) and Whole Genome Sequencing (WGS), combined with detailed phenotyping, can be used to find new genetic aetiologies for epilepsy
  2. To investigate whether NGS can be used to identify meaningful genetic modifiers for treatment response in patients with genetic epilepsy

  Methods:
  This project will involve doing NGS,including WGS, on i) Patients and their parents (trios) with presumed genetic epilepsy, or a developmental disorder known to be associated with epileptic seizures, to identify new genetic causes of epilepsy; and ii) Patients with pathogenic SCN1A mutations to identify genetic markers of treatment response. Recruitment will be from a cohort of patients referred to the West of Scotland epilepsy genetics service. Suitable participants will be identified from the service’s existing database. Detailed phenotypic information on each case will be obtained.

  Analysis:
  Analysis of variants found and ascertainment of their bio-functional consequences will take place in the genetics laboratory in Glasgow, and also in laboratories with whom we have a research agreement, including the Wellcome Trust Centre for Human Genetics (WTCHG) based at Oxford University. Whole Genome Sequencing, where performed, will be done at the WTCHG.

• REC name

  Scotland A REC

• REC reference

  16/SS/0054

• Date of REC Opinion

  15 Apr 2016

• REC opinion

  Further Information Favourable Opinion