Key result
Both loss-of-function and gain-of-function KCNQ5 mutations were associated with increased excitability and decreased repolarization reserve, leading to pathophysiology in four probands.
Case Report (n=4)
KCNQ5 mutations, both loss- and gain-of-function, are associated with intellectual disability and epileptic encephalopathy due to altered channel kinetics.
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KCNQ5 variants may cause refractory epilepsy with ID; leaves open validation and therapeutic targeting in larger cohorts.
KCNQ5 is a highly conserved gene encoding an important channel for neuronal function; it is widely expressed in the brain and generates M-type current. Exome sequencing identified de novo heterozygous missense mutations in four probands with intellectual disability, abnormal neurological findings, and treatment-resistant epilepsy (in two of four). Comprehensive analysis of this potassium channel for the four variants expressed in frog oocytes revealed shifts in the voltage dependence of activation, including altered activation and deactivation kinetics. Specifically, both loss-of-function and gain-of-function KCNQ5 mutations, associated with increased excitability and decreased repolarization reserve, lead to pathophysiology.
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Lehman et al. (2017) conducted a case report in Intellectual disability, abnormal neurological findings, and treatment-resistant epilepsy (n=4). KCNQ5 mutations was evaluated on Shifts in the voltage dependence of activation, including altered activation and deactivation kinetics. Both loss-of-function and gain-of-function KCNQ5 mutations were associated with increased excitability and decreased repolarization reserve, leading to pathophysiology in four probands.
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