Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
FEBS J. 2022 Dec;289(24):7776-7787. doi: 10.1111/febs.16204. Epub 2021 Sep 29.
The widespread availability of genetic testing for those with neurodevelopmental disorders has highlighted the importance of many genes necessary for the proper development and function of the nervous system. One gene found to be genetically altered in the X-linked intellectual disability disorder Claes-Jensen syndrome is KDM5C, which encodes a histone demethylase that regulates transcription by altering chromatin. While the genetic link between KDM5C and cognitive (dys)function is clear, how KDM5C functions to control transcriptional programs within neurons to impact their growth and activity remains the subject of ongoing research. Here, we review our current knowledge of Claes-Jensen syndrome and discuss important new data using model organisms that have revealed the importance of KDM5C in regulating aspects of neuronal development and function. Continued research into the molecular and cellular activities regulated by KDM5C is expected to provide critical etiological insights into Claes-Jensen syndrome and highlight potential targets for developing therapies to improve the quality of life of those affected.
神经发育障碍患者的基因检测广泛可用，这凸显了许多对神经系统正常发育和功能至关重要的基因的重要性。在 X 连锁智力障碍疾病克莱森综合征中发现一个基因发生遗传改变，这个基因是 KDM5C，它编码一种组蛋白去甲基化酶，通过改变染色质来调节转录。虽然 KDM5C 与认知（功能）障碍之间的遗传联系是明确的，但 KDM5C 如何控制神经元内的转录程序以影响其生长和活性仍然是正在进行的研究的主题。在这里，我们回顾了我们对克莱森综合征的现有认识，并讨论了使用模式生物的重要新数据，这些数据揭示了 KDM5C 在调节神经元发育和功能方面的重要性。对 KDM5C 调节的分子和细胞活动的进一步研究有望为克莱森综合征提供关键的病因学见解，并突出开发治疗方法的潜在靶点，以提高受影响者的生活质量。
