Sorbonne Université, INSERM, UMRS 938, Centre de Recherche Saint-Antoine, Paris, France.
AP-HP, Hôpital Trousseau, Service d'Explorations Fonctionnelles Endocriniennes, Paris, France.
Sci Adv. 2019 Feb 20;5(2):eaau9425. doi: 10.1126/sciadv.aau9425. eCollection 2019 Feb.
Imprinting disorders (IDs) often affect growth in humans, leading to diseases with overlapping features, regardless of the genomic region affected. IDs related to hypomethylation of the human 14q32.2 region and its domain are associated with Temple syndrome (TS14). TS14 is a rare type of growth retardation, the clinical signs of which overlap considerably with those of Silver-Russell syndrome (SRS), another ID related to down-regulation at 11p15.5 region. We show that 14q32.2 hypomethylation affects expression, not only for genes at this locus but also for other imprinted genes, and especially lowers levels at 11p15.5. Furthermore, expression of nonimprinted genes is also affected, some of which are also deregulated in SRS patients. These findings highlight the epigenetic regulation of gene expression at the domain. Expression profiling of TS14 and SRS patients highlights common signatures, which may account for the clinical overlap observed between TS14 and SRS.
印迹障碍（IDs）常影响人类的生长，导致具有重叠特征的疾病，而与受影响的基因组区域无关。与人类 14q32.2 区域及其 域的低甲基化相关的 IDs 与 Temple 综合征（TS14）有关。TS14 是一种罕见的生长迟缓类型，其临床特征与 Silver-Russell 综合征（SRS）重叠，SRS 也是另一种与 11p15.5 区域下调相关的 ID。我们表明，14q32.2 低甲基化不仅影响该基因座的基因表达，也影响其他印迹基因的表达，特别是降低 11p15.5 区域的水平。此外，非印迹基因的表达也受到影响，其中一些在 SRS 患者中也失调。这些发现强调了 域基因表达的表观遗传调控。对 TS14 和 SRS 患者的表达谱分析突出了共同的特征，这可能解释了 TS14 和 SRS 之间观察到的临床重叠。
