DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A/ KAT6B variants

Epigenomics. 2023 Mar;15(6):351-367. doi: 10.2217/epi-2023-0079. Epub 2023 May 30.

Abstract

Accurate diagnosis for patients living with neurodevelopmental disorders is often met with numerous challenges, related to the ambiguity of findings and lack of specificity in genetic variants leading to pathology. Genome-wide DNA methylation analysis has been used to develop highly sensitive and specific 'episignatures' as biomarkers capable of differentiating and classifying complex neurodevelopmental disorders. In this study we describe distinct episignatures for KAT6A syndrome, caused by pathogenic variants in the lysine acetyltransferase A gene (KAT6A), and for the two neurodevelopmental disorders associated with lysine acetyl transferase B (KAT6B). We demonstrate the ability of our models to differentiate between highly overlapping episignatures, increasing the ability to effectively identify and diagnose these conditions.

Keywords: DNA methylation; KAT6A; epigenetics; episignature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • DNA Methylation*
  • Histone Acetyltransferases / genetics
  • Humans
  • Neurodevelopmental Disorders* / genetics

Substances

  • Biomarkers
  • Histone Acetyltransferases
  • KAT6A protein, human
  • KAT6B protein, human