POGZ truncating alleles cause syndromic intellectual disability (White–Sutton syndrome)

White J et al., 2016: This seminal paper first described that truncating mutations in POGZ lead to a syndromic form of intellectual disability now known as White–Sutton syndrome. The authors identified five unrelated individuals with de novo POGZ truncating variants. All presented a strikingly similar phenotype: developmental delay, moderate-to-severe intellectual disability, hypotonia, distinctive facial features, short stature with obesity, and behavioral issues (autistic features in some). This consistent phenotype established POGZ as the causative gene. The study concluded that loss-of-function of POGZ defines a novel neurodevelopmental syndrome (later named White–Sutton syndrome). This discovery has since been confirmed by many others and expanded the understanding of POGZ’s role in human brain development.