A novel, de novo mutation in the PRKAG2 gene: infantile-onset phenotype and the signaling pathway involved.

ABSTRACT: PRKAG2 encodes the γ₂-subunit isoform of 5'-AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in the regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation, and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved, and therapeutic options for K475E mutation using cells stably expressing human wild-type (WT) or the K475E mutant. In human embryonic kidney-293 cells, the K475E mutation induced a marked increase in the basal phosphorylation of T

SUBMITTER: Xu Y 

PROVIDER: S-EPMC5582920 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature