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

Niels Vos, Jack Reilly, Mariet W. Elting, Philippe M. Campeau, David Coman, Zornitza Stark, Tiong Yang Tan, David J. Amor, Simran Kaur, Miya StJohn, Angela T. Morgan, Benjamin A. Kamien, Chirag Patel, Matthew L. Tedder, Giuseppe Merla, Paolo Prontera, Marco Castori, Kai Muru, Felicity Collins, John ChristodoulouJanine Smith, Bruria Ben Zeev, Alessandra Murgia, Emanuela Leonardi, Natacha Esber, Antonio Martinez-Monseny, Didac Casas-Alba, Matthew Wallis, Marcel Mannens, Michael A. Levy, Raissa Relator, Marielle Alders, Bekim Sadikovic

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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.
Original languageEnglish
Pages (from-to)351-367
Number of pages17
JournalEpigenomics
Volume15
Issue number6
DOIs
Publication statusPublished - 1 Mar 2023

Keywords

  • DNA methylation
  • KAT6A
  • epigenetics
  • episignature

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