Imprinting disorders
Imprinting disorders
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DOI：
10.1038/s41572-023-00443-4
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发表时间：
2023-06-29
影响因子：
81.5
通讯作者：
Elbracht，Miriam
中科院分区：
文献类型：
--
作者：
Eggermann，Thomas;Monk，David;Elbracht，Miriam
印迹障碍（ImpDis）是以基因组印迹紊乱为特征的先天性疾病。最常见的个体ImpD是Prader-Willi综合征、Angelman综合征和Beckwith-Wiedemann综合征。个体ImpDis具有相似的临床特征，如生长障碍和发育迟缓，但这些疾病是异质性的，关键的临床表现往往是非特异性的，使得诊断困难。影响差异甲基化区域（DMR）的四种类型的基因组和印迹缺陷（ImpDef）可引起ImpDis。这些缺陷会影响印记基因的单等位基因和亲本来源特异性表达。DMR内的调节以及它们的功能后果主要是未知的，但是已经确定了印记基因和功能通路之间的功能性串扰，从而深入了解了ImpDefs的病理生理学。ImpDis的治疗是对症的。由于这些疾病的罕见性，缺乏靶向治疗;然而，个性化治疗正在开发中。了解ImpDis的潜在机制，并改善这些疾病的诊断和治疗，需要多学科的方法与患者代表的投入。
Imprinting disorders (ImpDis) are congenital conditions that are characterized by disturbances of genomic imprinting. The most common individual ImpDis are Prader–Willi syndrome, Angelman syndrome and Beckwith–Wiedemann syndrome. Individual ImpDis have similar clinical features, such as growth disturbances and developmental delay, but the disorders are heterogeneous and the key clinical manifestations are often non-specific, rendering diagnosis difficult. Four types of genomic and imprinting defect (ImpDef) affecting differentially methylated regions (DMRs) can cause ImpDis. These defects affect the monoallelic and parent-of-origin-specific expression of imprinted genes. The regulation within DMRs as well as their functional consequences are mainly unknown, but functional cross-talk between imprinted genes and functional pathways has been identified, giving insight into the pathophysiology of ImpDefs. Treatment of ImpDis is symptomatic. Targeted therapies are lacking owing to the rarity of these disorders; however, personalized treatments are in development. Understanding the underlying mechanisms of ImpDis, and improving diagnosis and treatment of these disorders, requires a multidisciplinary approach with input from patient representatives.