RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia

Daniella Nishri, Hadassa Goldberg-Stern, Iris Noyman, Lubov Blumkin, Sara Kivity, Hirotomo Saitsu, Mitsuko Nakashima, Naomichi Matsumoto, Esther Leshinsky-Silver, Tally Lerman-Sagie, Dorit Lev*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Introduction Early onset epileptic encephalopathies (EOEEs) are a group of devastating diseases, manifesting in the first year of life with frequent seizures and/or prominent interictal epileptiform discharges on the electroencephalogram, developmental delay or regression and usually a poor prognosis. There are numerous causes for EOEEs making the diagnostic workup time consuming and costly. Methods We describe two siblings with fatal EOEE, profound global developmental delay and post-natal microcephaly that underwent extensive biochemical and metabolic workup in vain. Neuro-imaging disclosed non-specific progressive cerebral atrophy. Results Whole-exome sequencing (WES) disclosed compound heterozygous mutations in the gene encoding for mitochondrial arginyl-transfer RNA synthetase, RARS2. This gene has been previously described as the cause of pontocerebellar hypoplasia type 6. Conclusion We suggest that RARS2 gene mutations can cause a metabolic neurodegenerative disease manifesting primarily as EOEE with post-natal microcephaly, without the distinctive radiological features of pontocerebellar hypoplasia.

Original languageEnglish
Pages (from-to)412-417
Number of pages6
JournalEuropean Journal of Paediatric Neurology
Issue number3
StatePublished - 1 May 2016


FundersFunder number
Strategic Research Program for Brain Sciences11105137
challenging Exploratory Research26670505
Takeda Science Foundation
Japan Society for the Promotion of Science
Ministry of Education, Culture, Sports, Science and Technology12024421
Japan Science and Technology Agency
Ministry of Health, Labour and Welfare25293085, 13313587


    • Epileptic encephalopathy
    • Mitochondrial
    • Pontocerebellar hypoplasia
    • RARS2


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