Characterising the role of MID1 in X-linked Opitz syndrome: implications for CATCH22 and related disorders

奥皮茨综合征是一种使人衰弱的遗传性疾病，影响人类胚胎许多器官和组织的正常发育。Opitz综合征患者通常表现为面部畸形（如唇腭裂）以及生殖器和心脏缺陷。男性通常比女性受到更严重的影响，尽管疾病的严重程度甚至在同一家庭的男性之间也会有所不同。患者可能在婴儿期突然死亡，或因严重面部畸形导致的呼吸并发症和吞咽困难而遭受进一步的发育障碍。如果早期和经常重复的手术修复，不仅可以纠正面部畸形，还可以纠正任何心脏和生殖器异常，那么患者的前景将更加光明。我们的研究实验室最近发现了一种基因，当突变时，它会导致一种形式的奥皮茨综合征。这种基因的缺陷约占该疾病病例的一半。有证据表明，可能还有一些其他基因参与导致其余病例的疾病。这项拟议中的研究旨在调查由于基因突变而出错的分子和发育机制。预计这些研究将提供关于为什么一些患者比其他患者受到更严重影响的有价值的科学知识，并提供导致Opitz综合征剩余病例的基因身份的线索。这些结果对于理解其他表现出类似畸形的疾病也具有潜在的重要意义。从这项研究中获得的知识预计将为有进一步怀孕风险的家庭提供有效的遗传咨询（以及产前诊断的选择）提供宝贵的帮助。这也将最终导致受影响儿童更有效的疾病管理和矫正。

Opitz syndrome is a debilitating genetic disorder which affects the normal development of many organs and tissues of the human embryo. Patients with Opitz syndrome commonly present with facial deformities (such as cleft lip and palate) as well as both genital and heart defects. Males are usually more severely affected than females although the severity of the disease can vary even amongst males of the same family. Patients can die suddenly in infancy or suffer further developmental impairment due to respiratory complications and swallowing difficulties that result from the significant facial deformities. A brighter outlook for patients is expected if early and often repeated surgical repair is undertaken to correct not only the facial deformities but also any heart and genital abnormalities. Our research laboratory has recently identified the gene that, when mutated, causes one form of Opitz syndrome. Defects in this gene account for around half the cases with the disorder. Evidence suggests that there may be a number of other genes involved in causing the remaining cases of the disease. The proposed research is aimed at investigating the molecular and developmental mechanisms that go awry as a result of the gene mutation. It is anticipated that these studies will provide valuable scientific knowledge about why some patients are more severely affected than others as well as offering clues to the identity of the genes that cause the remaining cases of Opitz syndrome. The results also have potentially important implications for the understanding of other diseases that show similar deformities. The knowledge gained from this research is expected to provide a valuable aid for effective genetic counselling (as well as the option of prenatal diagnosis) for families at risk of further affected pregnancies. This will also ultimately lead to more effective disease management and correction in the affected child.