Koufaris Costas, Papagregoriou Gregoris, Kousoulidou Ludmila, Moutafi Maria, Tauber Maithé, Jouret Béatrice, Kieffer Isabelle, Deltas Constantinos, Tanteles George A, Anastasiadou Violetta, Patsalis Philippos C, Sismani Carolina
Department of Cytogenetics and Genomics, The Cyprus institute of Neurology and Genetics, Cyprus.
Department of Biological Sciences, University of Cyprus, Cyprus.
Gene. 2015 Apr 25;561(1):95-100. doi: 10.1016/j.gene.2015.02.018. Epub 2015 Feb 11.
MicroRNA haploinsufficiency has been associated with developmental defects in only a limited number of cases. Here we report a de novo genomic microdeletion that includes the LINGO2 gene as well as two microRNA genes, MIR873 and MIR876, in a patient with craniofacial abnormalities - in particular macrocephaly and hypertelorism - and learning difficulties. Subsequent analysis revealed that the microRNAs affected by this de novo microdeletion form a mammalian-lineage, neuronal tissue-enriched cluster. In addition, bioinformatic analysis and experimental data indicate that miR-873 is involved in the regulation of the Hedgehog signaling, an essential pathway involved in craniofacial patterning and differentiation. Collectively these observations are consistent with a role of the miR-873/miR-876 microRNA cluster in physiological cranial bone development and indicate that mutations affecting these microRNAs could be a rare cause of developmental defect in humans.
仅有少数病例显示，微小RNA单倍体不足与发育缺陷有关。在此，我们报告了一名患有颅面异常（特别是巨头畸形和眼距过宽）及学习困难的患者，其发生了一个新生的基因组微缺失，该微缺失包含LINGO2基因以及两个微小RNA基因MIR873和MIR876。后续分析表明，受此新生微缺失影响的微小RNA形成了一个在哺乳动物谱系中、富含于神经元组织的簇。此外，生物信息学分析和实验数据表明，miR - 873参与了刺猬信号通路的调控，这是一个在颅面模式形成和分化中起关键作用的信号通路。这些观察结果共同表明，miR - 873/miR - 876微小RNA簇在生理性颅骨发育中发挥作用，并提示影响这些微小RNA的突变可能是人类发育缺陷的一个罕见原因。
