Department of Psychiatry, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Psychiatry, Chang-Gung Memorial Hospital, Taoyuan, Taiwan.
J Formos Med Assoc. 2017 Oct;116(10):755-764. doi: 10.1016/j.jfma.2016.11.015. Epub 2017 Jan 9.
BACKGROUND/PURPOSE: Central nervous system (CNS) patterning genes are recognized as candidate genes for autism spectrum disorders (ASDs) based on neuroimaging and neuropathological evidence. Several genes that regulate CNS development are shown to be associated with ASD. Our previous family-based association study also revealed that a specific haplotype of WNT2 (wingless-type MMTV integration site family member 2) gene was overtransmitted to probands with ASD. Whether the CNS patterning genes moderate the clinical phenotype of ASD is unclear. This study investigated the genetic associations of WNT2, engrailed 2 (EN2), and forkhead box P2 (FOXP2) with the clinical symptom severity.
The sample included 391 patients (males, 88.3%; mean age±standard deviation, 9.5±4.4 years) diagnosed with ASDs. Tag single nucleotide polymorphisms (SNPs) of EN2, WNT2, and FOXP2 were genotyped. The single-locus and multilocus markers were tested for association.
We found that multilocus markers of WNT2 were associated with stereotyped behaviors whereas the markers of FOXP2 tended to be associated with social deficits. Moreover, an SNP of WNT2 showed a trend to be associated with less inattentive symptoms.
Our findings that WNT2 and FOXP2 may moderate the clinical phenotypes of ASD provide evidence to support the possible universal effect of WNT2 and FOXP2 on neurodevelopmental symptom dimensions. Such findings warrant further validation in other independent samples.
Clinical trial registration identifier: NCT00494754.
背景/目的：基于神经影像学和神经病理学证据，中枢神经系统（CNS）模式基因被认为是自闭症谱系障碍（ASD）的候选基因。有研究表明，一些调节 CNS 发育的基因与 ASD 有关。我们之前的基于家系的关联研究也表明，WNT2（无翅型 MMV 整合位点家族成员 2）基因的特定单倍型过度传递给 ASD 先证者。CNS 模式基因是否调节 ASD 的临床表型尚不清楚。本研究调查了 WNT2、EN2（ engrailed 2）和 FOXP2（叉头框 P2）基因与临床症状严重程度的遗传关联。
样本包括 391 名（男性，88.3%；平均年龄±标准差，9.5±4.4 岁）被诊断为 ASD 的患者。对 EN2、WNT2 和 FOXP2 的标签单核苷酸多态性（SNP）进行基因分型。对单基因座和多基因座标记进行关联检验。
我们发现 WNT2 的多基因座标记与刻板行为有关，而 FOXP2 的标记则与社会缺陷有关。此外，WNT2 的一个 SNP 与注意力不集中的症状较少有关。
我们发现 WNT2 和 FOXP2 可能调节 ASD 的临床表型，为 WNT2 和 FOXP2 对神经发育症状维度可能具有普遍影响提供了证据。这些发现需要在其他独立样本中进一步验证。
临床试验注册号：NCT00494754。
