Biallelic variants in the NARS2 gene are the cause of a continuous spectrum of neurodegenerative disorders presenting with various severity-from spastic paraplegia, progressive neurodegeneration to Leigh and Alpers syndrome. Common clinical signs result from a mitochondrial dysfunction based on OXPHOS deficiency. Here, we present a patient with infantile-onset severe epilepsy leading to fatal refractory status epilepticus. Whole exome sequencing with Exomiser analysis based on HPO terms detected two novel NARS2 variants in a compound heterozygous state. To date, 18 different NARS2 disease-causing mutations have been described. Our study adds to the understanding of this mitochondrial disorder.
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The study was supported by the MHCR AZV NU20-04-00279 and by RVO-VFN 64165 project of the Ministry of Health of the Czech Republic.
The study has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki), and the molecular genetic study was approved by the Institutional Review Board of the University Hospital Motol. Informed consent was obtained from both patient’s parents.
The authors declare no competing interests.
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Štěrbová, K., Vlčková, M., Hansíková, H. et al. Novel variants in the NARS2 gene as a cause of infantile-onset severe epilepsy leading to fatal refractory status epilepticus: case study and literature review. Neurogenetics 22, 359–364 (2021). https://doi.org/10.1007/s10048-021-00659-0
- Whole exome sequencing