We studied the phenotypic characteristics and the genome-wide DNA methylation in the peripheral blood samples of 20 individuals with heterozygous alterations in SIN3A. A total of 14 samples were used for the identification of the episignature and building of a predictive diagnostic biomarker, whereas the diagnostic model was used to investigate the methylation pattern of the remaining 6 samples.
A predominantly hypomethylated DNA methylation profile specific to WITKOS was identified, and the classifier model was able to diagnose a previously unresolved test case. The episignature was sensitive enough to detect individuals with varying degrees of phenotypic severity carrying SIN3A haploinsufficient variants.
We identified a novel, robust episignature in WITKOS due to SIN3A haploinsufficiency. This episignature has the potential to aid identification and diagnosis of individuals with WITKOS.
方法:我们研究了20例SIN3A杂合改变的个体外周血样本的表型特征和全基因组DNA甲基化。共有14个样本用于鉴定表观特征和建立预测性诊断生物标志物。而诊断模型用于研究其余6个样本的甲基化模式。
结果:鉴定出WITKOS特异性的主要低甲基化DNA甲基化谱,并且分类器模型能够诊断以前未解析的测试用例。表观特征足够灵敏以检测具有不同程度的表型严重性的携带SIN3A单倍体不足变体的个体。
结论:我们确定了一部小说,由于SIN3A单倍体不足,WITKOS中的鲁棒表观标记。这种表观特征有可能帮助识别和诊断患有WITKOS的个体。