Document Type
Article
Publication Date
4-19-2016
Abstract
Mutations in mitochondrial aminoacyl-tRNA synthetases are an increasingly recognized cause of human diseases, often arising in individuals with compound heterozygous mutations and presenting with system-specific phenotypes, frequently neurologic. FARS2 encodes mitochondrial phenylalanyl transfer ribonucleic acid (RNA) synthetase (mtPheRS), perturbations of which have been reported in 6 cases of an infantile, lethal disease with refractory epilepsy and progressive myoclonus. Here the authors report the case of juvenile onset refractory epilepsy and progressive myoclonus with compound heterozygous FARS2 mutations. The authors describe the clinical course over 6 years of care at their institution and diagnostic studies including electroencephalogram (EEG), brain magnetic resonance imaging (MRI), serum and cerebrospinal fluid analyses, skeletal muscle biopsy histology, and autopsy gross and histologic findings, which include features shared with Alpers-Huttenlocher syndrome, Leigh syndrome, and a previously published case of FARS2 mutation associated infantile onset disease. The authors also present structure-guided analysis of the relevant mutations based on published mitochondrial phenylalanyl transfer RNA synthetase and related protein crystal structures as well as biochemical analysis of the corresponding recombinant mutant proteins.
Recommended Citation
Walker, M.A., Mohler, K.P., Hopkins, K.W., Oakley, D.H., Sweetser, D.A., Ibba, M., Frosch, M.P. and Thibert, R.L. (2016) Novel compound heterozygous mutations expand the recognized phenotypes of FARS2-linked disease. J. Child Neurology 31, 1127-1137. https://doi.org10.1177/0883073816643402
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Biochemistry Commons, Cellular and Molecular Physiology Commons, Molecular Biology Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons, Other Biochemistry, Biophysics, and Structural Biology Commons
Comments
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Child Neurology, volume 31, in 2016 following peer review. The definitive publisher-authenticated version is available online at https://doi.org/10.1177/0883073816643402.