Key result
KCNB1 variant c.595A>T causes biophysical channel defects despite normal protein expression and trafficking.
Why the study?
A KCNB1 variant was identified in a proband with a neurodevelopmental disorder including epilepsy and centrotemporal spikes on EEG, requiring functional characterization.
The KCNB1 c.595A>T variant causes biophysical channel defects despite normal protein expression, suggesting a mechanism for the associated neurodevelopmental disorder.
Channel defects may explain KCNB1-related phenotypes; leaves open human validation before clinical translation.
OBJECTIVE: variant identified by clinical exome sequencing of a proband with a neurodevelopmental disorder that included epilepsy and centrotemporal spikes on EEG. METHODS: variant c.595A>T (p.Ile199Phe). Biochemical and electrophysiologic experiments were performed to determine whether this variant affected protein expression, trafficking, and channel functional properties. RESULTS: Biochemical characterization of the variant suggested normal protein expression and trafficking. Functional characterization revealed biophysical channel defects in assembled homotetrameric and heterotetrameric channels. CONCLUSIONS: variants, suggesting the possibility that the degree of KCNB1 protein dysfunction may influence disease severity.
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Calhoun et al. (2017) studied Neurodevelopmental disorder, autism, intellectual disability, and epilepsy (n=1). KCNB1 variant c.595A>T (p.Ile199Phe) was evaluated on Protein expression, trafficking, and channel functional properties. The KCNB1 variant c.595A>T (p.Ile199Phe) exhibited normal protein expression and trafficking but caused biophysical channel defects in assembled homotetrameric and heterotetrameric channels.
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