KCNQ2 R144 variants cause neurodevelopmental disability with language impairment and autistic features without neonatal seizures through a gain-of-function mechanism.

ABSTRACT:

Background

Prior studies have revealed remarkable phenotypic heterogeneity in KCNQ2-related disorders, correlated with effects on biophysical features of heterologously expressed channels. Here, we assessed phenotypes and functional properties associated with KCNQ2 missense variants R144W, R144Q, and R144G. We also explored in vitro blockade of channels carrying R144Q mutant subunits by amitriptyline.

Methods

Patients were identified using the RIKEE database and through clinical collaborators. Phenotypes were collected by a standardized questionnaire. Functional and pharmacological properties of variant subunits were analyzed by whole-cell patch-clamp recordings.

Findings

Detailed clinical information on fifteen patients (14 novel and 1 previously published) was analy

SUBMITTER: Miceli F 

PROVIDER: S-EPMC9254340 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature