Novel splice site mutation in EIF2AK3 gene causes Wolcott-Rallison syndrome in a consanguineous family from Saudi Arabia

摘要

The Wolcott-Rallison syndrome (WRS, OMIM 226980) is a rare condition in which patients are characterized by infancy-onset diabetes mellitus and multiple epiphyseal dysplasia (Wolcott and Rallison 1972). Loss of function mutations in a eukaryotic translation initiation factor 2-alpha kinase-3 (EIF2AK3 OMIM 604032) gene known as pancreatic PKR-like endoplasmic reticulum kinase (PERK) have been reported as underlying genetic cause of WRS (Delepine et al. 2000). The permanent neonatal diabetes mellitus (PNDM) in consanguineous WRS families have been reported mostly in Arabs (Julier and Nicolino 2010; Habeb et al. 2015; Deeb et al. 2016). The function of PERK has been detected to initiate the cellular response to endoplasmic reticulum stress; failure of which causes accumulation of misfolded proteins leading to cell damage or apoptosis (Harding et al. 2001; Zhang et al. 2002). Institutional Review Board (IRB) of Medical Research and Ethics, King Abdulaziz University, Jeddah approved the study according Helsinki's Declaration.