Characterization of KCNB1 variants associated with infantile epilepsy

Epilepsy is the fourth most common neurological disease in the United States, affecting approximately 4% of individuals during their lifetime. Seizure itself is a devastating symptom for patients and their family, and may result in long-term consequences if poorly controlled. Our understanding on the neurophysiology of epileptic seizures is yet incomplete, and thus some seizures are not treatable with currently available therapies. A significant portion of human epilepsy is caused by genetic factors which cause malfunctioning of ion channels that should tightly and rapidly control our brain network. Mutations in the KCNB1 gene have been reported in epileptic patients who suffer seizures since their infancy and childhood. KCNB1 encodes channels that conduct potassium ion, which is a very critical ion for cellular communications in the brain. Accumulating evidence suggests that not all KCNB1 mutations are the equivalent. Each KCNB1 mutation may have a differential effect in the brain at cellular and molecular level. In the proposed study, we will investigate how a series of KCNB1 mutations identified in patients affects channel protein function. The results of this study will allow us to gain valuable insights for developing animal models of KCNB1-related epilepsy, as well as for development of novel therapies that may improve seizure control and quality of life for patients with KCNB1 mutations.