Expanding the genotype-phenotype spectrum in SCN8A-related disorders
Malavika Hebbar1, Nawaf Al-Taweel1, Inderpal Gill1
1Division of Neurology, Department of Pediatrics, BC Children's Hospital, Faculty of Medicine, University of British Columbia, Vancouver BC.
Background:
SCN8A-related disorders are a group of variable conditions caused by pathogenic variations in SCN8A. Online Mendelian Inheritance in Man (OMIM) terms them as developmental and epileptic encephalopathy 13, benign familial infantile seizures 5 or cognitive impairment with or without cerebellar ataxia.
Methods:
In this study, we describe clinical and genetic results on eight individuals from six families with SCN8A pathogenic variants identified via exome sequencing.
Results:
Clinical findings ranged from normal development with well-controlled epilepsy to significant developmental delay with treatment-resistant epilepsy. Three novel and three reported variants were observed in SCN8A. Electrophysiological analysis in transfected cells revealed a loss-of-function variant in Patient 4.
Conclusions:
This work expands the clinical and genotypic spectrum of SCN8A-related disorders and provides electrophysiological results on a novel loss-of-function SCN8A variant.
More Related Videos
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
00:06In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Related Concept Videos
01:33Pleiotropy
01:28Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
02:26Comparing Copy Number Variations and SNPs
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
01:43Sex-linked Disorders
01:11Genetic Lingo
01:27Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...