ZOLD Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome
Publication: Springer Link | Publication Date: March 26, 2020
Authors: K. Batjargal, T. Tajima, E. F. Jimbo & T. Yamagata
Abstract
Purpose
Wolfram syndrome (WS) is a rare disorder caused by mutations in WFS1 that is characterized by diabetes mellitus, optic atrophy, sensorineural deafness, diabetes insipidus, and neurodegeneration. This disease is usually inherited as an autosomal recessive trait, but an autosomal dominant form has been reported. WFS1 encodes a transmembrane protein, which is a maintenance component of endoplasmic homeostasis. These dominant mutations were thought to increase endoplasmic reticulum (ER) stress. Recent studies suggest that 4-phenylbutyrate (PBA) and valproate (VPA) reduce ER stress. The objective of this study was to analyze the effect of PBA and VPA on dominant WFS1 mutants in vitro.