Alfonso Manuel D'Alessio

1 Introduction Protein O-GlcNAcylation is a highly conserved post-translational modification consisting of the addition of N-acetylglucosamine (GlcNAc) on protein serines and threonines (Yang and Qian 2017). More than 5000 proteins have been shown to be O-GlcNAcylated (Wulff-Fuentes et al. 2021), and they participate in the regulation of a wide range of functions (Butkinaree et al. 2010; Ferrer et al. 2014).

A homozygous truncating variant in PDCD6IP was recently reported in two siblings with primary microcephaly, intellectual disability, and short stature from a consanguineous Saudi family [1]. Although additional unrelated cases are lacking, microcephaly observed in Pdcd6ip knockout mice [2, 3] and pdcd6ip knockdown zebrafish [4] supports the pathogenicity of PDCD6IP loss-of-function variants.