Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature
Frameshift mutations at the C-terminus of HIST1H1E result in a specific DNA hypomethylation signature
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DOI：
10.1186/s13148-019-0804-0
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发表时间：
2020-01-07
影响因子：
5.7
通讯作者：
Tartaglia, Marco
中科院分区：
文献类型：
--
作者：
Ciolfi, Andrea;Aref-Eshghi, Erfan;Tartaglia, Marco
背景我们先前将导致Rahman综合征的HIST1H1E突变与特定的全基因组甲基化模式联系起来。结果6例受影响受试者外周血样本的甲基化组分析使我们确定了一个特定的低甲基化谱。这种“附加标记”富含参与神经系统发育和功能的基因。计算分类器在检测拉赫曼综合征受试者中产生了完全的灵敏度和特异性。将该模型应用于未确诊的先证者队列，使我们能够在一个受试者中达到诊断。结论：我们在Rahman综合征受试者中证明了一种表观遗传标记，可用于分子诊断。
Background We previously associated HIST1H1E mutations causing Rahman syndrome with a specific genome-wide methylation pattern. Results Methylome analysis from peripheral blood samples of six affected subjects led us to identify a specific hypomethylated profile. This "episignature" was enriched for genes involved in neuronal system development and function. A computational classifier yielded full sensitivity and specificity in detecting subjects with Rahman syndrome. Applying this model to a cohort of undiagnosed probands allowed us to reach diagnosis in one subject. Conclusions We demonstrate an epigenetic signature in subjects with Rahman syndrome that can be used to reach molecular diagnosis.