[P1-99] De Novo SCN8A Mutation Identified by Whole-Exome Sequencing in a Boy With Early-Onset Epileptic Encephalopathy and movement Disorders
Objective: Mutations in SCN8A, a voltage-gated sodium-channel type VIII alpha subunit gene, have recently been recognized as one of the pathogenic mechanisms leading to Early-Onset Epileptic Encephalopathies (EOEEs). We aimed to report a de novo heterozygous missense mutation (c.4423 G>A, p.Gly1475Arg) in SCN8A gene in a patient of EOEEs.
Methods: Whole-exome sequencing of a parent-offspring trio was used to identify the cause of EOEE in a boy with infantile seizures refractory to multiple antiepileptic drugs, movement disorders, and severe Intellectual disability. The boy died at the age f 25 months because of sudden unexpected death in epilepsy (SUDEP).
Results: A de novo heterozygous missense mutation (c.4423 G>A, p.Gly1475Arg) in SCN8A gene was identified. In silico analysis using bwa-0.7.10, picard-tools-1.119, Samtools1.0, GATK3.2, PolyPhen-2.2.2 and Annovar suggested that the mutation has a deleterious effect on protein function. Also, the affected amino acid is located at the extremely conserved position at the intracellular linker between domains III and IV of the alpha subunits of voltage-gated sodium channels, which is responsible for fast inactivation of the channel.
Significance: A new mutation in SCN8A gene was reported suggesting additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies
Methods: Whole-exome sequencing of a parent-offspring trio was used to identify the cause of EOEE in a boy with infantile seizures refractory to multiple antiepileptic drugs, movement disorders, and severe Intellectual disability. The boy died at the age f 25 months because of sudden unexpected death in epilepsy (SUDEP).
Results: A de novo heterozygous missense mutation (c.4423 G>A, p.Gly1475Arg) in SCN8A gene was identified. In silico analysis using bwa-0.7.10, picard-tools-1.119, Samtools1.0, GATK3.2, PolyPhen-2.2.2 and Annovar suggested that the mutation has a deleterious effect on protein function. Also, the affected amino acid is located at the extremely conserved position at the intracellular linker between domains III and IV of the alpha subunits of voltage-gated sodium channels, which is responsible for fast inactivation of the channel.
Significance: A new mutation in SCN8A gene was reported suggesting additional investigations will be worthwhile to determine the prevalence and contribution of SCN8A mutations to epileptic encephalopathies