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. [1]

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 [2]. The present finding of de novo KCNB1 mutations as a cause of K2.1 dysfunction expands the locus heterogeneity associated with epileptic encephalopathies [3].