Aminoacyl tRNA synthetases (ARSs) are highly conserved enzymes that link amino acids to their cognate tRNAs. Thirty-seven ARSs are known and their deficiencies cause various genetic disorders. Variants in some ARSs are associated with the autosomal dominant inherited form of axonal neuropathy, including Charcot-Marie-Tooth (CMT) disease. Variants of genes encoding ARSs often cause disorders in an autosomal recessive fashion. The clinical features of cytosolic ARS deficiencies are more variable, including systemic features. Deficiencies of ARSs localized in the mitochondria are often associated with neurological disorders including Leigh and early-onset epileptic syndromes. Whole exome sequencing (WES) is an efficient way to identify the genes causing various symptoms in patients. We identified 4 pedigrees with novel compound heterozygous variants in ARS genes (WARS1, MARS1, AARS2, and PARS2) by WES. Some unique manifestations were noted. The number of patients with ARSs has been increasing since the application of WES. Our findings broaden the known genetic and clinical spectrum associated with ARS variants.
Keywords: AARS2; Aminoacyl tRNA synthetases; MARS1; PARS2; WARS1.
© 2021. Fondazione Società Italiana di Neurologia.