Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialities "G. D'Alessandro," University of Palermo, Palermo, Italy.
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Mol Genet Genomic Med. 2022 May;10(5):e1911. doi: 10.1002/mgg3.1911. Epub 2022 Mar 29.
This study was aimed to analyze the commonalities and distinctions of voltage-gated sodium channels, Nav1.2, Nav1.6, in neurodevelopmental disorders. An observational study was performed including two patients with neurodevelopmental disorders. The demographic, electroclinical, genetic, and neuropsychological characteristics were analyzed and compared with each other and then with the subjects carrying the same genetic variants reported in the literature. The clinical features of one of them argued for autism spectrum disorder and developmental delay, the other for intellectual disability, diagnoses confirmed by the neuropsychological assessment. The first patient was a carrier of SCN2A (p.R379H) variant while the second was carrier of SCN8A (p.E936K) variant, both involving the pore loop of the two channels. The results of this study suggest that the neurodevelopmental disorders without overt epilepsy of both patients can be the consequences of loss of function of Nav1.2/Nav1.6 channels. Notably, the SCN2A variant, with an earlier expression timing in brain development, resulted in a more severe phenotype as autism spectrum disorder and developmental delay, while the SCN8A variant, with a later expression timing, resulted in a less severe phenotype as intellectual disability.
本研究旨在分析电压门控钠离子通道 Nav1.2、Nav1.6 在神经发育障碍中的共性和差异。进行了一项观察性研究，纳入了两名患有神经发育障碍的患者。分析并比较了他们的人口统计学、电临床、遗传学和神经心理学特征，然后与文献中报道的携带相同遗传变异的受试者进行了比较。其中一名患者的临床特征为自闭症谱系障碍和发育迟缓，另一名患者的诊断为智力障碍，这两种障碍均通过神经心理学评估得到了确认。第一位患者是 SCN2A（p.R379H）变异的携带者，第二位患者是 SCN8A（p.E936K）变异的携带者，这两种变异均涉及两种通道的孔环。本研究结果表明，这两名患者均无明显癫痫的神经发育障碍可能是 Nav1.2/Nav1.6 通道功能丧失的结果。值得注意的是，SCN2A 变异在大脑发育中的表达时间更早，导致更为严重的表型，如自闭症谱系障碍和发育迟缓，而 SCN8A 变异在大脑发育中的表达时间较晚，导致较轻的表型，如智力障碍。
