Aminoacylation‐defective bi‐allelic mutations in human <scp>EPRS1</scp> associated with psychomotor developmental delay, epilepsy, and deafness
Danni Jin, Sheree A. Wek, Ricardo A. Cordova, Ronald C. Wek, Didier Lacombe, Vincent Michaud, Karin Musier‐Forsyth
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.
Topics & Concepts
Missense mutationLeukodystrophyAminoacyl tRNA synthetaseGeneticsEpilepsyAminoacylationAlleleCompound heterozygosityBiologyMutationMedicineDiseaseTransfer RNAInternal medicineNeuroscienceGeneRNARNA and protein synthesis mechanismsRNA modifications and cancerRNA Research and Splicing