From the Department of Pediatrics, Hainan Women and Children's Medical Center, Hainan, China.
From the Department of Pediatrics, Hainan Women and Children's Medical Center, Hainan, China
J Psychiatry Neurosci. 2023 Sep 6;48(5):E334-E344. doi: 10.1503/jpn.230046. Print 2023 Sep-Oct.
Over recent decades, autism spectrum disorder (ASD) has been of increasing epidemiological importance, given the substantial increase in its prevalence; at present, clinical diagnosis is possible only after 2 years of age. In this study, we sought to develop a potential predictive model for ASD screening.
We conducted a longitudinal follow-up study of newborns over 3 years. We measured transcript levels of 4 genes (superoxide dismutase-2 [], retinoic acid-related orphan receptor-α [], G protein-coupled estrogen receptor-1 [], progesterone receptor []), 2 oxidative stress markers and epigenetic marks at the promoter in case-control umbilical cord blood mononuclear cell (UCBMC) samples.
We followed 2623 newborns; we identified 41 children with ASD, 63 with delayed development and 2519 typically developing children. We matched the 41 children with ASD to 41 typically developing children for UCBMC measurements. Our results showed that children with ASD had significantly higher levels of H3K9me3 histone modifications at the promoter and oxidative stress in UCBMC than typically developing children; children with delayed development showed no significant differences. Children with ASD had significantly lower expression of , and , but higher expression than typically developing children. We established a model based on these 4 candidate genes, and achieved an area under the curve of 87.0% (standard deviation 3.9%) with a sensitivity of 1.000 and specificity of 0.854 to predict ASD in UCBMC.
Although the gene combinations produced a good pass/fail cut-off value for ASD evaluation, relatively few children in our study sample had ASD.
The altered gene expression in UCBMC can predict later autism development, possibly providing a predictive model for ASD screening immediately after birth.
近年来，自闭症谱系障碍（ASD）的发病率不断上升，具有重要的流行病学意义；目前，只有在 2 岁以后才能进行临床诊断。本研究旨在建立一种 ASD 筛查的潜在预测模型。
我们对新生儿进行了 3 年的纵向随访研究。我们测量了 4 个基因（超氧化物歧化酶 2 [SOD2]、维甲酸相关孤儿受体-α [RORA]、G 蛋白偶联雌激素受体 1 [GPER1]、孕激素受体 [PR]）、2 个氧化应激标志物和启动子上的表观遗传标记在病例对照脐带血单核细胞（UCBMC）样本中的转录水平。
我们随访了 2623 名新生儿；发现 41 名 ASD 儿童、63 名发育迟缓儿童和 2519 名正常发育儿童。我们将 41 名 ASD 儿童与 41 名正常发育儿童进行 UCBMC 测量匹配。结果显示，ASD 儿童 UCBMC 中的 H3K9me3 组蛋白修饰和氧化应激水平明显高于正常发育儿童；发育迟缓儿童无显著差异。ASD 儿童的 、 和 表达水平明显较低，但 表达水平较高。我们基于这 4 个候选基因建立了一个模型，在 UCBMC 中预测 ASD 的曲线下面积为 87.0%（标准差 3.9%），灵敏度为 1.000，特异性为 0.854。
尽管基因组合产生了良好的 ASD 评估通过/失败截断值，但我们研究样本中 ASD 儿童相对较少。
UCBMC 中基因表达的改变可以预测自闭症的后续发展，可能为出生后立即进行 ASD 筛查提供预测模型。
