Department of Human Pathology of the Adult and Developmental Age "Gaetano Barresi", Unit of Child Neurology and Psychiatry, University of Messina.
Department of Biomedical Sciences and Morphological and Functional, University of Messina, Messina, Italy.
Epileptic Disord. 2018 Oct 1;20(5):423-427. doi: 10.1684/epd.2018.0992.
De novo mutations in the GRIN1 gene have been recently reported as the molecular cause of a broad-spectrum early-onset neurological phenotype. Here, we describe a five-year-old girl with an early-onset epileptic encephalopathy associated with an infantile hyperkinetic movement disorder and oculomotor abnormalities. Whole-exome sequencing identified a novel p.Met641Leu de novo variant in the GRIN1 gene as the cause of the phenotype. In silico analysis suggested that the p.Met641Leu variant would alter the gating property of the ion channel, with the involved methionine residue facing towards the ion pore. Long-term systematic video-EEG allowed us to report on the electroclinical history and, specifically, on the semiology of the hyperkinetic movement disorder and oculomotor abnormalities resembling oculogyric crises in our patient. Our findings and a review of the recent literature reinforce the notion of GRIN1-encephalopathy as a recognizable neurological phenotype that should be suspected in early-onset epilepsy associated with hyperkinetic movement disorders. [Published with video sequence on www.epilepticdisorders.com].
最近有报道称，GRIN1 基因中的新生突变是一种广泛的早发性神经表型的分子病因。在这里，我们描述了一例 5 岁女孩，患有早发性癫痫性脑病，伴有婴儿期多动障碍和眼球运动异常。全外显子组测序发现 GRIN1 基因中的一个新的 p.Met641Leu 新生变异是该表型的原因。计算机分析表明，p.Met641Leu 变异会改变离子通道的门控特性，涉及的蛋氨酸残基朝向离子通道。长期系统的视频脑电图使我们能够报告电临床病史，特别是我们患者的多动障碍和眼球运动异常的半侧症状，类似于眼球震颤危象。我们的发现和对最近文献的回顾加强了 GRIN1-脑病作为一种可识别的神经表型的概念，在伴有多动障碍的早发性癫痫中应怀疑存在这种疾病。[在 www.epilepticdisorders.com 上发布带有视频序列]。
