Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC). The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions. Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.

中文翻译：

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系统生物学方法描绘健康个体和特纳综合征个体之间血液单核细胞的表达差异

特纳综合征 (TS) 是一种罕见的疾病，与女性一条 X 染色体完全或部分丢失有关。关于 TS 基因型-表型关系的信息不充分。比较健康患者和特纳综合征患者可能有助于阐明 TS 病理生理学机制。使用加权基因共表达网络分析 (WGCNA) 的系统生物学方法对 182 份微阵列外周单核血样本 (PBMC) 来表征健康人和特纳综合征个体之间的基因表达差异。健康和 TS 的共表达网络具有无标度拓扑，确保网络的鲁棒性。在此过程中，健康者和TS之间保留了5个模块，每个模块都携带了几个共同的基因。其中两个，SMCHD1 和 PGK1，已被报道与 TS 相关。之前报道的 TS 基因，特别是 PTPN22、RPS4X、CSF2RA 和 TIMP1，在各自的模块中缺失。这些基因的功能障碍、差异表达或缺失可能导致分子途径的逐渐破坏，从而导致 TS 的病理生理学。事实上，在健康样本和 TS 样本之间进行比较时，我们观察到这些模块的功能存在显着差异。我们在 PPI 网络中确定了四个簇，这些簇是由富含重要功能的前 15 个 KME 构建的。总体而言，我们的工作强调了 TS 的潜在分子功能、途径和分子靶标，可在人类医疗保健系统中进行治疗。