Functional characterization of a GFAP variant of uncertain significance in an Alexander disease case within the setting of an individualized medicine clinic

Abstract

A de novo GFAP variant, p.R376W, was identified in a child presenting with hypotonia, developmental delay, and abnormal brain MRI . Following the 2015 ACMG variant classification guidelines and the functional studies showing protein aggregate formation in vitro, p.R376W should be classified as a pathogenic variant, causative for Alexander disease.