Aminoacylation-defective bi-allelic mutations in human EPRS1 associated with psychomotor developmental delay,epilepsy, and deafness |
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| Authors: | Danni Jin Sheree A. Wek Ricardo A. Cordova Ronald C. Wek Didier Lacombe Vincent Michaud Karin Musier-Forsyth |
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| Affiliation: | 1. Department of Chemistry and Biochemistry, Center for RNA Biology, Ohio State University, Columbus, Ohio, USA;2. Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA;3. Department of Medical Genetics, University Hospital of Bordeaux, Bordeaux, France |
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| Abstract: | Aminoacyl-tRNA synthetases are enzymes that ensure accurate protein synthesis. Variants of the dual-functional cytoplasmic human glutamyl-prolyl-tRNA synthetase, EPRS1, have been associated with leukodystrophy, diabetes and bone disease. Here, we report compound heterozygous variants in EPRS1 in a 4-year-old female patient presenting with psychomotor developmental delay, seizures and deafness. Functional studies of these two missense mutations support major defects in enzymatic function in vitro and contributed to confirmation of the diagnosis. |
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| Keywords: | aminoacylation aminoacyl-tRNA synthetase EPRS1 exome sequencing integrated stress response leukodystrophy psychomotor developmental delay tRNA |
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