Compound heterozygous mutation of the IARS2 gene: a rare cause of Leigh Syndrome

Abstract

Described in 2005 by Bonnefond, L. et al, IARS2 (OMIM 612801) is a mitochondrial isoleucyl-tRNA synthetase encoded in the nucleus. Phenotypically, the mutation in the IARS2 is expressed in a broad clinical spectrum, which includes Leigh Syndrome (LS) as well as extra-neurological effects. We described a 7-year-old boy who presented global developmental delay, hypotonia and epilepsy, evolving with epileptic encephalopathy. An MRI showed diffuse brain atrophy and areas of capsular changes bilaterally, while the exome showed compound heterozygous mutation in the IARS2 gene, a probable pathogenic variant inherited from the mother - p.[(Arg201His)], and a pathogenic variant inherited from the father - p.[(Trp520*)]. In the literature, we found 11 cases of patients who presented phenotypically as LS with mutation of the IARS2 gene. This report shows a patient with pathogenic variants never described in IARS2 compound heterozygosity, reinforcing the hypothesis of association of the IARS2 gene with this syndrome.