Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome.

ABSTRACT:

Aims

More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients.

Methods and results

We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter

SUBMITTER: Aizawa T 

PROVIDER: S-EPMC10105889 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature