• Molecules and Cells
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• v.22 no.2
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• pp.127-132
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• 2006

In the post genome project era, it is well established that the human genome contains a smaller number of genes than expected. The complexity found in higher organisms can be explained if proteins are multifunctional. Indeed, recent studies are continuing to reveal proteins that are capable of a broad repertoire of functions. A good paradigm for multifunctionality can be found in the amino-acyl tRNA synthetases (aaRSs), an ancient conserved family of proteins. This unique family, which is comprised of 20 different enzymes, is well known for its participation in protein synthesis. Several studies have described numerous examples of these "housekeeping" proteins taking part in extensive critical cellular activities. In this review, we focus on a member of that family, lysyl-tRNA synthetase (LysRS), which has been shown to have a dual functionality. In addition to its contribution to the translation process, LysRS also takes part in the regulation of MITF and USF2 target genes. This phenomenon was first described in mast cells.

• Journal of Genetic Medicine
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• v.16 no.2
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• pp.55-61
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• 2019

Purpose: Genetic defects in the nuclear-encoded mitochondrial aminoacyl-tRNA synthetases were first identified as causes of various disorders in 2007. Variants in IARS2, which encodes a mitochondrial isoleucyl-tRNA synthetase, were first reported in 2014. These variants are associated with diverse phenotypes ranging from CAGSSS (CAtaracts, Growth hormone deficiency, Sensory neuropathy, Sensorineural hearing loss, and Skeletal dysplasia) and Leigh syndrome to isolated nonsyndromic cataracts. Here, we describe the phenotypic and genetic spectrum of Korean patients with IARS2-related disorders. Materials and Methods: Using whole-exome sequencing followed by Sanger sequencing, we identified five patients with IARS2 mutations. Their medical records and brain magnetic resonance images were reviewed retrospectively. Results: All five patients presented with developmental delay or regression before 18 months of age. Three patients had bilateral cataracts, but none had hearing loss or sensory neuropathy. No evidence of skeletal dysplasia was noted, but two had short stature. One patient had cardiomyopathy and another exhibited renal tubulopathy and hypoparathyroidism. Their brain imaging findings were consistent with Leigh syndrome. Interestingly, we found the recurrent mutations p.R817H and p.V105Dfs*7 in IARS2. Conclusion: To our knowledge, this is the first report of Korean patients with IARS2-related disorders. Our findings broaden the phenotypic and genotypic spectrum of IARS2-related disorders in Korea and will help to increase clinical awareness of IARS2-related neurodegenerative diseases.