Abstract

Abstract Pathogenic variants of polycomb repressive complex‐2 (PRC2) subunits are associated with overgrowth syndromes and neurological diseases. EZH2 is a major component of PRC2 and mediates the methylation of H3K27 trimethylation (H3K27me3). Germline variants of EZH2 have been identified as a cause of Weaver syndrome (WS), an overgrowth/intellectual disability (OGID) syndrome characterized by overgrowth, macrocephaly, accelerated bone age, intellectual disability (ID), and characteristic facial features. Germline variants of SUZ12 and EED , other components of PRC2, have also been reported in the WS or Weaver‐like syndrome. EZH1 is a homolog of EZH2 that interchangeably associates with SUZ12 and EED . Recently, pathogenic variants of EZH1 have been reported in individuals with dominant and recessive neurodevelopmental disorders. We herein present sisters with biallelic loss‐of‐function variants of EZH1 . They showed developmental delay, ID, and central precocious puberty, but not the features of WS or other OGID syndromes.