Human KCNQ5 de novo mutations underlie epilepsy and intellectual disability

作者：Aguan Wei, Paul Wakenight, Theresa A. Zwingman, Angela M. Bard, Nikhil Sahai, Marjolein H. Willemsen, Helenius J. Schelhaas, Alexander P.A. Stegmann, Judith Verhoeven, de Man, Marja W. Wessels, Tjitske Kleefstra, Deepali N. Shinde, Katherine L. Helbig, Alice Basinger, Victoria F. Wagner, David Rodriguez‐Buritica, Emily Bryant, J Gordon Millichap, Kathleen J. Millen, William B. Dobyns, Jan‐Marino Ramirez, Franck Kalume · 发表于：Journal of Neurophysiology · 年份：2022 · DOI：10.1152/jn.00509.2021 · 被引用次数：20 · 研究领域：Ion channel regulation and function、Cardiac electrophysiology and arrhythmias、Genetics and Neurodevelopmental Disorders

Six novel de novo human KCNQ5 variants were identified from children with neurodevelopmental delay, intellectual disability, and/or epilepsy. Expression of these variants along with four previously reported KCNQ5 variants from a similar cohort revealed GOF potassium channels, negatively shifted in V 50 of activation and/or delayed deactivation kinetics. GOF is extended to KCNQ5/3 heteromeric channels, making these the predominant channels affected in heterozygous de novo patients. Kcnq5 LOF mice exhibited seizures, consistent with in vivo pathogenicity.