The molecular genetic mechanism of Turner syndrome (TS) still leaves much to be discovered. Methods: TS (45X0) patients and age-matched controls (46XX and 46XY) were selected. The nanopore sequencing combined with trio-whole exome sequencing (trio-WES) were used for the first time to investigate TS. Results: Thirteen TS (45X0) patients and eight controls were enrolled. Trio-WES analysis did not find any pathogenetic or likely pathogenic variants except X chromosome (chrX) deletion. The average methylation levels and patterns of chrX in 45X0 and 46XY were similar, and significantly higher than in 46XX (p = 2.22 × 10⁻¹⁶). Both hyper-methylation and hypo-methylation were detected in the CpG island (CGI), CGI_shore, promoter, genebody, and PAR1-region, while in the transposon element inactivation regions of the chrX and hypermethylation were predominant. A total of 125 differentially methylated genes were identified in 45X0 compared to 46XX, including 8 and 117 hypermethylated and hypomethylated genes, respectively, with the enrichment terms of mitophagy, regulation of DNA-binding transcription factor activity, etc. Conclusions: The results suggest that the methylation profile in patients with TS might be determined by the number of X chromosomes; the patterns of methylation in TS were precisely associated with the maintenance of genomic stability and improvement of gene expression. Differentially methylated genes/pathways might reveal the potential epigenetic modulation and lead to better understanding of TS.

中文翻译：

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纳米孔测序确定的特纳综合征 X 染色体 DNA 高甲基化和特定甲基化谱

特纳综合征 (TS) 的分子遗传机制仍有许多有待发现。方法：选择 TS（45X0）患者和年龄匹配的对照（46XX 和 46XY）。纳米孔测序结合三全外显子组测序 (trio-WES) 首次用于研究 TS。结果：招募了 13 名 TS (45X0) 患者和 8 名对照。Trio-WES 分析未发现除 X 染色体 (chrX) 缺失外的任何致病性或可能的致病性变异。45X0 和 46XY 中 chrX 的平均甲基化水平和模式相似，并且显着高于 46XX ( p = 2.22 × 10 ^-16）。在 CpG 岛 (CGI)、CGI_shore、启动子、基因体和 PAR1 区域中检测到高甲基化和低甲基化，而在 chrX 的转座子元件失活区域和高甲基化中占主导地位。与 46XX 相比，45X0 和 46XX 共鉴定出 125 个差异甲基化基因，其中高甲基化和低甲基化基因分别为 8 个和 117 个，富集条件包括线粒体自噬、DNA 结合转录因子活性的调节等。结论：结果表明TS 患者的甲基化谱可能由 X 染色体的数量决定；TS中的甲基化模式与维持基因组稳定性和改善基因表达精确相关。