Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy
Loss-of-Function Mutations in FRRS1L Lead to an Epileptic-Dyskinetic Encephalopathy
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DOI：
10.1016/j.ajhg.2016.04.008
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发表时间：
2016-06-02
影响因子：
9.8
通讯作者：
Kruer, Michael C.
中科院分区：
文献类型：
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作者：
Madeo, Marianna;Stewart, Michelle;Kruer, Michael C.
谷氨酸能神经传递支配哺乳动物大脑中的兴奋性信号传导，并且已显示谷氨酸信号传导的异常有助于癫痫和多动性运动障碍。许多严重的儿童期运动障碍和癫痫的病因仍然没有特征。我们描述了一种神经系统疾病与癫痫和突出的舞蹈手足徐动症所造成的双等位基因致病变异FRRS1L，编码AMPA受体外核心蛋白。FRRS1L功能的丧失减弱了AMPA介导的电流，暗示了这种儿童单基因神经系统疾病中的多巴胺能神经传递的慢性异常。
Glutamatergic neurotransmission governs excitatory signaling in the mammalian brain, and abnormalities of glutamate signaling have been shown to contribute to both epilepsy and hyperkinetic movement disorders. The etiology of many severe childhood movement disorders and epilepsies remains uncharacterized. We describe a neurological disorder with epilepsy and prominent choreoathetosis caused by biallelic pathogenic variants in FRRS1L, which encodes an AMPA receptor outer-core protein. Loss of FRRS1L function attenuates AMPA-mediated currents, implicating chronic abnormalities of glutamatergic neurotransmission in this monogenic neurological disease of childhood.