Distinct expression requirements and rescue strategies for BEST1 loss- and gain-of-function mutations.

ABSTRACT: Genetic mutation of the human BEST1 gene, which encodes a Ca²⁺-activated Cl^- channel (BEST1) predominantly expressed in retinal pigment epithelium (RPE), causes a spectrum of retinal degenerative disorders commonly known as bestrophinopathies. Previously, we showed that BEST1 plays an indispensable role in generating Ca²⁺-dependent Cl^- currents in human RPE cells, and the deficiency of BEST1 function in patient-derived RPE is rescuable by gene augmentation (Li et al., 2017). Here, we report that BEST1 patient-derived loss-of-function and gain-of-function mutations require different mutant to wild-type (WT) molecule ratios for phenotypic manifestation, underlying their distinct epigenetic requirements in bestrophinopathy development,

SUBMITTER: Zhao Q 

PROVIDER: S-EPMC8169119 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature