The detailed molecular mechanism of orbital venous malformation (OVM) is still not clear. Using whole exome sequencing, 4 types of melanocortin 4 receptor (MC4R) mutation were detected in 7 of 27 patients with OVM, and all types of MC4R mutations resulted in the upregulation of MC4R expression. In vitro study indicated that MC4R has impacts on the proliferation, cell cycle, migration, and tube formation of the endothelial cells. Moreover, MC4R mutations altered the downstream signaling, including cAMP concentration and the expression levels of several PI3K/AKT/mTOR downstream genes, including p21, cyclin B1, ITGA10, and ITGA11. MC4R mutations may lead to the pathogenesis of OVM through modulating the downstream signaling to alter the angiogenic activity of endothelial cells.

中文翻译：

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MC4R的突变促进了眼眶静脉畸形患者的血管生成活性。

眼眶静脉畸形（OVM）的详细分子机制仍不清楚。使用全外显子组测序，在27例OVM患者中有7位检测到4种类型的黑皮质素4受体（MC4R）突变，所有类型的MC4R突变均导致MC4R表达上调。体外研究表明，MC4R对内皮细胞的增殖，细胞周期，迁移和管形成有影响。此外，MC4R突变改变了下游信号传导，包括cAMP浓度和几个PI3K / AKT / mTOR下游基因的表达水平，包括p21，cyclin B1，ITGA10和ITGA11。MC4R突变可能通过调节下游信号以改变内皮细胞的血管生成活性而导致OVM的发病。