Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.
Department of Pathology & Laboratory Medicine, Western University, London, ON, N6A 5C1, Canada.
Epigenomics. 2023 Mar;15(6):351-367. doi: 10.2217/epi-2023-0079. Epub 2023 May 30.
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 (), and for the two neurodevelopmental disorders associated with lysine acetyl transferase B (). We demonstrate the ability of our models to differentiate between highly overlapping episignatures, increasing the ability to effectively identify and diagnose these conditions.
对于患有神经发育障碍的患者，准确的诊断通常会遇到许多挑战，这与发现结果的模糊性以及导致病理的遗传变异缺乏特异性有关。全基因组 DNA 甲基化分析已被用于开发高度敏感和特异的“表观遗传特征”作为生物标志物，能够区分和分类复杂的神经发育障碍。在这项研究中，我们描述了 KAT6A 综合征的独特表观遗传特征，其由赖氨酸乙酰转移酶 A 基因 () 中的致病性变异引起，以及与赖氨酸乙酰转移酶 B 相关的两种神经发育障碍 ()。我们证明了我们的模型区分高度重叠的表观遗传特征的能力，从而提高了有效识别和诊断这些疾病的能力。
