DNA Methylation Signature for EZH2 Functionally Classifies Sequence Variants in Three PRC2 Complex Genes

Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2, which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism.

Source: The American Journal of Human Genetics - April 1, 2020 Category: Genetics & Stem Cells Authors: Sanaa Choufani, William T. Gibson, Andrei L. Turinsky, Brian H.Y. Chung, Tianren Wang, Kopal Garg, Alessandro Vitriolo, Ana S.A. Cohen, Sharri Cyrus, Sarah Goodman, Eric Chater-Diehl, Jack Brzezinski, Michael Brudno, Luk Ho Ming, Susan M. White, Sally Ann Tags: Article Source Type: research