DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A / KAT6B variants.
Niels VosJack ReillyMariet W EltingPhilippe M CampeauDavid ComanZornitza StarkTiong Yang TanDavid J AmorSimran KaurMiya StJohnAngela T MorganBenjamin A KamienChirag PatelMatthew L TedderGiuseppe MerlaPaolo PronteraMarco CastoriKai MuruFelicity CollinsJohn ChristodoulouJanine SmithBruria Ben ZeevAlessandra MurgiaEmanuela LeonardiNatacha EsberAntonio Martinez-MonsenyDidac Casas-AlbaMatthew WallisMarcel M A M MannensMichael A LevyRaissa RelatorMarielle AldersBekim SadikovicPublished in: Epigenomics (2023)
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.
Keyphrases
- genome wide
- dna methylation
- copy number
- end stage renal disease
- gene expression
- ejection fraction
- newly diagnosed
- chronic kidney disease
- peritoneal dialysis
- prognostic factors
- magnetic resonance imaging
- patient reported outcomes
- congenital heart disease
- amino acid
- tandem mass spectrometry
- magnetic resonance
- fluorescent probe
- molecularly imprinted