47,XXX (triple X) and Turner syndrome (45,X) are sex chromosomal abnormalities with detrimental effects on health with increased mortality and morbidity. In karyotypical normal females, X‐chromosome inactivation balances gene expression between sexes and upregulation of the X chromosome in both sexes maintain stoichiometry with the autosomes. In 47,XXX and Turner syndrome a gene dosage imbalance may ensue from increased or decreased expression from the genes that escape X inactivation, as well as from incomplete X chromosome inactivation in 47,XXX. We aim to study genome‐wide DNA‐methylation and RNA‐expression changes can explain phenotypic traits in 47,XXX syndrome. We compare DNA‐methylation and RNA‐expression data derived from white blood cells of seven women with 47,XXX syndrome, with data from seven female controls, as well as with seven women with Turner syndrome (45,X). To address these questions, we explored genome‐wide DNA‐methylation and transcriptome data in blood from seven females with 47,XXX syndrome, seven females with Turner syndrome, and seven karyotypically normal females (46,XX). Based on promoter methylation, we describe a demethylation of six X‐chromosomal genes (AMOT , HTR2C , IL1RAPL2 , STAG2 , TCEANC , ZNF673 ), increased methylation for GEMIN8 , and four differentially methylated autosomal regions related to four genes (SPEG , MUC4 , SP6 , and ZNF492 ). We illustrate how these changes seem compensated at the transcriptome level although several genes show differential exon usage. In conclusion, our results suggest an impact of the supernumerary X chromosome in 47,XXX syndrome on the methylation status of selected genes despite an overall comparable expression profile.

中文翻译：

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47，XXX综合征中过量X染色体物质的表观遗传和转录组后果-与特纳综合征和46，XX雌性的比较。

47，XXX（三倍X）和特纳综合征（45，X）是性染色体异常，对健康有害，死亡率和发病率增加。在核型正常的女性中，X染色体失活平衡了两性之间的基因表达，并且两性中X染色体的上调维持了常染色体的化学计量。在47，XXX和Turner综合征中，基因剂量失衡可能是由于逃避X灭活的基因表达的增加或减少以及47，XXX中X染色体失活引起的。我们旨在研究全基因组的DNA甲基化和RNA表达的变化，可以解释47，XXX综合征的表型特征。我们比较了来自7名47，XXX综合征的女性白细胞的DNA甲基化和RNA表达数据，以及来自7名女性对照的数据，以及7名患有特纳综合征的女性（45，X）。为解决这些问题，我们探讨了来自7名47，XXX综合征的女性，7名Turner综合征的女性和7名核型正常的女性（46，XX）血液中全基因组DNA甲基化和转录组数据。基于启动子甲基化，我们描述了六个X染色体基因的去甲基化（AMOT，HTR2C，IL1RAPL2，STAG2，TCEANC，ZNF673）增加了GEMIN8的甲基化程度，并增加了与四个基因（SPEG，MUC4，SP6和ZNF492）相关的四个差异甲基化的常染色体区域。我们阐明了这些变化在转录组水平上似乎如何得到补偿，尽管几个基因显示出不同的外显子用法。总之，我们的结果表明47，XXX综合征中的X染色体对所选基因的甲基化状态有影响，尽管总体表达水平相当。