Abstract
VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase. Mutations in VARS2 have recently been identified as a cause of mitochondrial encephalomyopathy in three individuals. However, clinical information remained scarce. Exome sequencing lead us to identify compound heterozygous pathogenic VARS2 variants in a boy presenting with severe lactic acidosis, hypertrophic cardiomyopathy, epilepsy, and abnormalities on brain imaging including hypoplasia of corpus callosum and cerebellum as well as a massive lactate peak on MR-spectroscopy. Studies in patient-derived fibroblasts confirmed the functional relevance of the identified VARS2 variants. Our report expands the phenotypic spectrum associated with this rare mitochondrial defect, in that VARS2 deficiency may also cause severe neonatal presentations with cardiac involvement and structural brain abnormalities.
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Abbreviations
- EEG:
-
electroencephalography
- mt-aaRS:
-
mitochondrial aminoacyl-tRNA-synthetases
- MRI:
-
magnetic resonance imaging
- OXPHOS:
-
oxidative phosphorylation
- SDS-PAGE:
-
Sodium dodecyl polyacrylamide gel electrophoresis
- MRS:
-
magnetic resonance spectroscopy
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This project was supported by the BMBF funded German Network for Mitochondrial Disorders (mitoNET #01GM1113C) and by the E-Rare project GENOMIT (01GM1207). TBH was supported by the BMBF through the Juniorverbund in der Systemmedizin “mitOmics” (FKZ 01ZX1405C). FD was supported by a grant of the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University Düsseldorf. FB was supported by a fellowship of the German Research Foundation/Deutsche Forschungsgemeinschaft (BA 5758/1–1).
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Baertling, F., Alhaddad, B., Seibt, A. et al. Neonatal encephalocardiomyopathy caused by mutations in VARS2 . Metab Brain Dis 32, 267–270 (2017). https://doi.org/10.1007/s11011-016-9890-2
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DOI: https://doi.org/10.1007/s11011-016-9890-2