A Novel CNTNAP2 Mutation Results in Abnormal Neuronal E/I Balance.
A Novel CNTNAP2 Mutation Results in Abnormal Neuronal E/I Balance.
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一种新的 CNTNAP2 突变导致神经元 E/I 平衡异常
DOI：
10.3389/fneur.2021.712773
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发表时间：
2021
影响因子：
3.4
通讯作者：
Zheng H
中科院分区：
文献类型：
--
作者：
Lu P;Wang F;Zhou S;Huang X;Sun H;Zhang YW;Yao Y;Zheng H
CNTNAP 2（编码蛋白Caspr 2）是neurexin家族的成员，在兴奋性和抑制性突触后电流的平衡（E/I平衡）中起重要作用。在这里，我们描述了一个新的致病性错义突变的婴儿自发性复发性癫痫发作（SRS）和智力残疾。基因检测显示CNTNAP 2基因中存在错义突变c.2329 C>G（p.R777G）。为了探索这种新的突变的影响，原代培养的神经元转染野生型homo CNTNAP 2或R777 G突变，并评估神经元的形态和功能。与溶剂对照组或野生型组相比，CNTNAP 2 R777 G突变组的神经突和膜电流，包括自发兴奋性突触后电流（sEPSC）和抑制性突触后电流（sIPSC）均减少或减弱。CNTNAP 2 R777 G组动作电位（AP）也明显受损。因此，CNTNAP 2 R777 G可能导致神经网络中兴奋性和抑制性突触后电流的失衡，从而导致SRS。
CNTNAP2 (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 CNTNAP2 gene. To explore the effect of this novel mutation, primary cultured neurons were transfected with wild type homo CNTNAP2 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 CNTNAP2 R777G mutation group were all decreased or weakened. Moreover, the action potentials (APs) were also impaired in CNTNAP2 R777G group. Therefore, CNTNAP2 R777G may lead to the imbalance of excitatory and inhibitory post-synaptic currents in neural network contributing to SRSs.
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影响因子：
10.6
作者：
Foss-Feig JH;Adkinson BD;Ji JL;Yang G;Srihari VH;McPartland JC;Krystal JH;Murray JD;Anticevic A
通讯作者：
Anticevic A
影响因子：
3.7
作者：
Gatto CL;Broadie K
通讯作者：
Broadie K
影响因子：
14.8
作者：
Beaudoin, Gerard M. J., III;Lee, Seung-Hye;Arikkath, Jyothi
通讯作者：
Arikkath, Jyothi
影响因子：
16.2
作者：
Lohmann, Christian;Bonhoeffer, Tobias
通讯作者：
Bonhoeffer, Tobias
影响因子：
11
作者：
Gao R;Piguel NH;Melendez-Zaidi AE;Martin-de-Saavedra MD;Yoon S;Forrest MP;Myczek K;Zhang G;Russell TA;Csernansky JG;Surmeier DJ;Penzes P
通讯作者：
Penzes P