Clinical and functional heterogeneity associated with the disruption of retinoic acid receptor beta.

ABSTRACT:

Purpose

Dominant variants in the retinoic acid receptor beta (RARB) gene underlie a syndromic form of microphthalmia, known as MCOPS12, which is associated with other birth anomalies and global developmental delay with spasticity and/or dystonia. Here, we report 25 affected individuals with 17 novel pathogenic or likely pathogenic variants in RARB. This study aims to characterize the functional impact of these variants and describe the clinical spectrum of MCOPS12.

Methods

We used in vitro transcriptional assays and in silico structural analysis to assess the functional relevance of RARB variants in affecting the normal response to retinoids.

Results

We found that all RARB variants tested in our assays exhibited either a gain-of-function or a loss-of-function activity

SUBMITTER: Caron V 

PROVIDER: S-EPMC10757562 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature