WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome.

ABSTRACT:

Background

Wolfram syndrome (WFS) is a rare disorder characterised by childhood-onset diabetes mellitus and progressive optic atrophy. Most patients have variants in the WFS1 gene. We undertook functional studies of WFS1 variants and correlated these with WFS1 protein expression and phenotype.

Methods

9 patients with a clinical diagnosis of WFS were studied with quantitative PCR for markers of endoplasmic reticulum (ER) stress and immunoblotting of fibroblast protein extracts for WFS1 protein expression. Luciferase reporter assay was used to assess ATF-6 dependent unfolded protein response (UPR) activation.

Results

6 patients with compound heterozygous nonsense mutations in WFS1 had no detectable WFS1 protein expression; 3 patients with missense v

SUBMITTER: Hu K 

PROVIDER: S-EPMC8685651 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature