Researchers at Scripps Research Institute, San Diego, and other centers in California; Johns Hopkins, Baltimore; Vanderbilt University, TN; and Northwestern University Feinberg School of Medicine, Chicago, IL; searched for de novo mutations in a family with a sporadic case of epileptic encephalopathy. The cause was determined using whole exome sequencing (WES) and whole genome sequencing (WGS). A de novo missense mutation in KCNB1 was identified that encodes the K2.1 voltage-gated potassium channel. Subsequently, 2 additional patients were identified with epileptic encephalopathy and de novo KCNB1 missense mutations that cause a similar pattern of K2.1 dysfunction. Clinical WES may be useful for diagnosis of epileptic encephalopathies of unknown etiology. 
COMMENTARY. Researchers at University of Arizona, Tucson, previously explored the utility of WES and identified causal de novo variants in genes of 7 of 10 children with sporadic epilepsy, refractory seizures, developmental delay, or epileptic encephalopathy. These probands all presented with seizures within the first 6 months of life, and 6 have intractable seizures. The genes affected included SCN1A, CDKL5, EEF1A2, and KCNH5 . The present finding of de novo KCNB1 mutations as a cause of K2.1 dysfunction expands the locus heterogeneity associated with epileptic encephalopathies .