Key result
The KCNQ2 missense variants p.(N258K) and p.(G279D) significantly impaired Kv7.2 M-current amplitude and surface membrane expression, demonstrating loss-of-function and dominant-negative effects.
Why the study?
KCNQ2 mutations cause infantile-onset epileptic disorders with variable functional effects requiring different therapies, necessitating more patient reports and elucidated molecular mechanisms to clarify genotype-phenotype correlations.
Population
104 patients with infantile-onset pharmacoresistant epilepsy
Design
Genetic sequencing and in vitro functional study
Authors
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Case reports refine KCNQ2 phenotypic spectrum; leaves open functional classification for therapy selection.
Observational (n=9)
No
The novel p.(G279D) and recently reported p.(N258K) KCNQ2 variants cause neonatal-onset seizures through loss-of-function and dominant-negative effects on Kv7.2 potassium channels.
Chokvithaya et al. (2023) conducted an observational in KCNQ2-related neonatal seizures (n=9). KCNQ2 missense variants (p.(N258K) and p.(G279D)) vs. Wild-type KCNQ2 was evaluated on Electrophysiological function and cellular localization of Kv7.2 channels. The KCNQ2 missense variants p.(N258K) and p.(G279D) significantly impaired Kv7.2 M-current amplitude and surface membrane expression, demonstrating loss-of-function and dominant-negative effects.
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