Commonalities and distinctions between two neurodevelopmental disorder subtypes associated with SCN2A and SCN8A variants and literature review

Molecular Genetics & Genomic Medicine

Rosaria Nardello¹  Mario Giuffrè¹  Vincenzo Antona¹  Giuseppe Donato Mangano¹  Antonina Fontana¹  Vincenzo Salpietro²  Giuseppa Renata Mangano³ 

[1] 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;Department of Psychology, Educational Sciences and Human Movement University of Palermo Palermo Italy;

关键词: autism spectrum disorders;    EEG;    epilepsy;    intellectual disability;    SCN2A;    SCN8A;   

DOI  :  10.1002/mgg3.1911

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown