A recurrent de novo variant supports KCNC2 involvement in the pathogenesis of developmental and epileptic encephalopathy

Am J Med Genet A. 2021 Nov;185(11):3384-3389. doi: 10.1002/ajmg.a.62455. Epub 2021 Aug 27.

Abstract

Developmental and epileptic encephalopathies (DEE) are a heterogenous group of conditions characterized by the co-occurrence of epilepsy and intellectual/developmental disability. Despite several known DEE-related genes, including these encoding ion channels, still many cases remain without molecular diagnosis. Here, we present a 2-year-old girl with severe DEE in whom whole exome sequencing revealed de novo p.(Val471Leu) variant in the KCNC2 encoding Kv3.2, a voltage-gated potassium channel. To the best of our knowledge, this is the third DEE case due to KCNC2 mutation. Our clinical and molecular findings, particularly the recurrence of p.(Val471Leu) in patient with similar clinical phenotype, further support KCNC2 as a novel DEE-associated gene.

Keywords: KCNC2; developmental and epileptic encephalopathy; recurrent de novo variant; whole exome sequencing.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Diseases / genetics*
  • Brain Diseases / physiopathology
  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • Epilepsy
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Mutation, Missense / genetics
  • Phenotype
  • Shaw Potassium Channels / genetics*

Substances

  • KCNC2 protein, human
  • Shaw Potassium Channels