Identification of novel disease genes in rare sib pairs with epileptic encephalopathies.

Epilepsy is the fourth most common neurological disorder, affecting around 50 million of people worldwide. While 70% of individuals with epilepsy respond well to currently available anti-epileptic drugs, one third of people continues to present seizures despite multiple drug trials. Understanding the underlying causes and mechanisms of epilepsy is an important step for the development of novel treatments. The epileptic encephalopathies (EEs) are a heterogeneous subgroup of severe epilepsies with onset in the first years of life, which are characterized by treatment resistant seizures and developmental slowing or regression. The majority of EEs have a monogenic basis, and recent advances in gene discovery have greatly increased our neurobiological insights in these disorders. Nevertheless, the genetic cause of around 60-70% of EEs still remains unknown. In this project, we will conduct whole exome sequencing on a collection of very rare affected sib pairs with EEs in which mutations in known genes have been excluded previously. We thus will uncover novel genes for EE, improve diagnostics, and increase our understanding of the mechanisms leading to the disease. This is indispensable for future novel targeted treatment development, a much needed task for these severe disorders that are highly drug resistant.

Keywords:EXOME SEQUENCING, EPILEPTIC ENCEPHALOPATHIES, GENETICS

Disciplines:Genetics, Systems biology, Laboratory medicine, Molecular and cell biology, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other clinical sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences