The identification of the disease -causing mutations in genes associated with episodic coma in a family with three girls affected with this disorder using Next Generation Sequencing (NGS)

The present study reports a case of familial episodic coma in which three girls manifesting refractory seizures followed by coma. Targeted gene panel of epilepsy using next-generation sequencing (NGS) technique was requested to identified disease -causing variant(s) in the patients.

After obtaining a written informed consent from our patient, genomic DNA was extracted from venous blood, for identifying mutations in epilepsy genes, at first, coding regions as well as all intron–exon boundaries of the 72 genes were captured by Sure Select Target Enrichment System V4 kit (Agilent, Santa Clara, CA), then captured libraries were sequenced on an Illumina HiSeq 4000(Illumina Inc., San Diego, CA, USA), sequenced reads were aligned with a reference human genome and Picard tools was used to remove duplicated reads; variant calling was performed using the Genome Analysis Tool Kit (GATK). ANNOVAR was used to annotated variants, then all variants were filtered out based on minor allele frequency (MAF) <1 % according to data bases of nucleotide including dpSNP, 1000 Genome project. In silico tools was performed to evaluated pathogenicity of variant(s).

According to databases of pathogenicity prediction of gene, no specific mutation in epilepsy genes was found in our patients, but several polymorphisms were reported.

Given polymorphisms in genes related to epilepsy were found in our study, failed to provide us with an acceptable diagnosis of this condition, further research is needed to reveal the cause of the disease.