Clinical whole-exome sequencing reveals a novel missense pathogenic variant of GNAO1 in a patient with infantile-onset epilepsy

Abstract Background The cause of infantile-onset epilepsy is complex and is not easily recognized clinically, particularly in paediatric patients who present with non-specific neurological signs, no radiological abnormalities and no metabolic changes. Case We report a case of infantile-onset epilepsy in a 10-month-old Chinese girl who presented with non-specific neurological signs, no radiological abnormalities and no biochemical disturbances. She first presented at birth with twitching movements and convulsions of an unknown aetiology. Ambulatory EEG showed epileptic rhythmic activities, the presence of asynchrony and runs of sharp waves over the right parietal and central areas. Given the non-specific neurological features and negative structural and biochemical findings, we applied clinical whole-exome sequencing (WES) to determine the underlying aetiology. WES revealed a novel heterozygous missense pathogenic variant, GNAO1 :NM_020988.2:c.118G > A; NP_066268.1:p.Gly40Arg. A genetic analysis of the family confirmed the variant identified is a de novo mutation. Conclusions Clinical WES can streamline genetic analysis and sort out pathogenic genes in an unbiased approach. GNAO1 is a disease-causing gene for the autosomal dominant form of early infantile epileptic encephalopathy. The novel pathogenic variant identified in this case should contribute to our understanding of the expanding spectrum of infantile-onset epilepsy.