Novel IARS2 mutations in Japanese siblings with CAGSSS, Leigh, and West syndrome

Abstract Background IARS2 encodes isoleucine-tRNA synthetase, which is aclass-1 amino acyl-tRNA synthetase. IARS2 mutations are reported to cause Leigh syndrome or cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysphasia syndrome (CAGSSS). To our knowledge, IARS2 mutations and diseases related to it have only been reported in three families. Here we report a case of two Japanese siblings with Leigh syndrome, some features of CAGSSS, and West syndrome that are found to have compound heterozygous novel IARS2 mutations. Case report A 7-month-old Japanese girl presented with infantile spasms. Brain magnetic resonance imaging (MRI) revealed diffuse brain atrophy and hyperintensity in the bilateral basal ganglia. Three years later, her younger sister also presented with infantile spasms. MRI revealed diffuse brain atrophy and hyperintensity of the bilateral ganglia, suggesting Leigh syndrome. The siblings were identified with compound heterozygous missense mutations in IARS2 , p.[(Phe227Ser)];[(Arg817His)]. Conclusion This is the first case study reporting Leigh syndrome concomitant with some features of CAGSSS in siblings with novel IARS2 mutations, thereby broadening the phenotypic spectrum of IARS2 -related disorders. Further studies are warranted to elucidate the nature of these disorders.