Retinopathy and optic atrophy: Expanding the phenotypic spectrum of pathogenic variants in the AARS2 gene

Ophthalmic Genet. 2018 Jan-Feb;39(1):99-102. doi: 10.1080/13816810.2017.1350723. Epub 2017 Aug 18.


Background: Optic atrophy may be the sequela of optic nerve injury due to any insult, including isolated and syndromic genetic diseases. Alanyl-tRNA synthetase 2 (AARS2) pathogenic variants have been reported to cause leukodystrophy with ovarian failure, and cardiomyopathy (#615889) as well as combined oxidative phosphorylation deficiency-8 (#614096). We report a young child who presented with decreased vision due to optic atrophy and was found to harbor missense variants in the AARS2 gene expanding the phenotypic expression of the AARS2 gene.

Materials and methods: Single observational case report with genetic testing, laboratory testing, neurologic and ophthalmic clinical examinations, and neuroimaging performed at a tertiary academic medical center.

Results: An 18-month old Korean boy was noted to have a progressive decline in visual function. The physical exam revealed bilateral optic atrophy, peripheral retinal bone spicule pigmentation, and absent patellar reflexes. Electromyography was consistent with demyelinating polyneuropathy. Magnetic resonance imaging (MRI) of the brain and spine showed cerebellar and supratentorial white matter multifocal changes with areas of restricted diffusion, and dorsal column signal abnormalities. Whole exome sequencing revealed two missense variants in the AARS2 gene [c.1519G>C (p.V507L) and c.2165G>A (p.R722Q)], found to be in trans on parental testing.

Conclusions: Missense variants in the AARS2 gene are the likely cause of the retinopathy and optic atrophy in this patient. This finding expands the phenotypic spectrum of the AARS2 gene.

Keywords: AARS2; leukodystrophy; optic atrophy; retinopathy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Alanine-tRNA Ligase / genetics*
  • Child, Preschool
  • Exome Sequencing
  • Genetic Testing
  • Humans
  • Leukoencephalopathies / diagnostic imaging
  • Leukoencephalopathies / genetics
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense*
  • Optic Atrophy / diagnosis
  • Optic Atrophy / genetics*
  • Phenotype
  • Retinal Diseases / diagnosis
  • Retinal Diseases / genetics*
  • Visual Acuity / physiology


  • Alanine-tRNA Ligase