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


METHODS
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.
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Chun-Yiu
CY
Law
Department of Pathology, The University of Hong Kong, Hong Kong, China.
Sharon Tzu-Lun
ST
Chang
Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Korea.
Sun Young
SY
Cho
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.
Eric Kin-Cheong
EK
Yau
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.
Grace Sui-Fun
GS
Ng
Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong, China.
Nai-Chung
NC
Fong
Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
Ching-Wan
CW
Lam
D017668:Age of Onset; D004827:Epilepsy / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D006801:Humans; D007223:Infant; D020125:Mutation, Missense / Q000235:genetics*; D017422:Sequence Analysis, DNA
C584143:GNAO1 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
Clinical whole-exome sequencing; Early infantile epileptic encephalopathy; GNAO1