Lu Ping, Wang Fengpeng, Zhou Shuixiu, Huang Xiaohua, Sun Hao, Zhang Yun-Wu, Yao Yi, Zheng Honghua
Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, China.
Jiangsu Province Hospital of Integrated Chinese and Western Medicine, Nanjing, China.
Front Neurol. 2021 Oct 19;12:712773. doi: 10.3389/fneur.2021.712773. eCollection 2021.
(coding for protein Caspr2), a member of the neurexin family, plays an important role in the balance of excitatory and inhibitory post-synaptic currents (E/I balance). Here, we describe a novel pathogenic missense mutation in an infant with spontaneous recurrent seizures (SRSs) and intellectual disability. Genetic testing revealed a missense mutation, c.2329 C>G (p. R777G), in the gene. To explore the effect of this novel mutation, primary cultured neurons were transfected with wild type homo or R777G mutation and the morphology and function of neurons were evaluated. When compared with the vehicle control group or wild type group, the neurites and the membrane currents, including spontaneous excitatory post-synaptic currents (sEPSCs) and inhibitory post-synaptic currents (sIPSCs), in R777G mutation group were all decreased or weakened. Moreover, the action potentials (APs) were also impaired in R777G group. Therefore, R777G may lead to the imbalance of excitatory and inhibitory post-synaptic currents in neural network contributing to SRSs.
（编码蛋白Caspr2）是神经连接蛋白家族的一员，在兴奋性和抑制性突触后电流平衡（E/I平衡）中起重要作用。在此，我们描述了一名患有自发性癫痫发作（SRSs）和智力残疾的婴儿中的一种新型致病性错义突变。基因检测在该基因中发现了一个错义突变，c.2329 C>G（p.R777G）。为了探究这种新型突变的影响，将野生型同源物或R777G突变转染到原代培养的神经元中，并评估神经元的形态和功能。与载体对照组或野生型组相比，R777G突变组的神经突以及膜电流，包括自发性兴奋性突触后电流（sEPSCs）和抑制性突触后电流（sIPSCs），均减少或减弱。此外，R777G组的动作电位（APs）也受损。因此，R777G可能导致神经网络中兴奋性和抑制性突触后电流失衡，从而导致SRSs。
