Whole-genome sequencing of a cohort of 30 adults with unexplained developmental and epileptic encephalopathies in Qaiser et al., 2021 identified three individuals with potentially pathogenic KCNA2 variants; all three of these patients presented with seizures, intellectual disability, and autism spectrum disorder. Autism spectrum disorder has previously been reported in a subset of individuals with KCNA2-associated movement disorders (Helbig et al., 2016; Ngo et al., 2020). An inherited frameshift variant in KCNA2 has also been identified in an ASD proband from the iHART cohort (Ruzzo et al., 2019).
Molecular Function
Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. It belongs to the delayed rectifier class, members of which allow nerve cells to efficiently repolarize following an action potential. Heterozygous mutations in this gene are responsible for a form of developmental and epileptic encephalopathy [Developmental and epileptic encephalopathy 32 (DEE32); OMIM 6163
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Genome sequencing identifies rare tandem repeat expansions and copy number variants in Lennox-Gastaut syndrome
