KMT2A and KMT2B episignatures address diagnostic challenges associated with rare neurodevelopmental disorders

Pathogenic variants in KMT2A and KMT2B, encoding histone H3 lysine 4 methyltransferases, cause distinct neurodevelopmental disorders—Wiedemann-Steiner syndrome (WDSTS) and Dystonia 28 (DYT28), respectively. We generated and validated DNA methylation (DNAm) signatures for both disorders using cohorts with truncating and missense variants.