Novel AARS2 gene mutation producing leukodystrophy: a case report

J Hum Genet. 2017 Feb;62(2):329-333. doi: 10.1038/jhg.2016.126. Epub 2016 Oct 13.


AARS2 gene (NM_020745.3) mutations result in two different phenotypic diseases: infantile mitochondrial cardiomyopathy and late-onset leukoencephalopathy. The patient's first symptoms appeared at the age of 18 years with behavioral changes and psychiatric problems. Some years later, extrapyramidal symptoms, cognitive impairment, nystagmus, dysarthria and pyramidal symptoms also developed. The brain magnetic resonance imaging (MRI) indicated extensive white matter abnormalities. The diagnosis of AARS2 gene mutations causing leukodystrophy was confirmed by genetic testing. Segregation analysis confirmed the compound heterozygous state of the patient. Histological examination of the biopsy did not prove specific pathological alterations. The clinical phenotype of our patient was compared with seven previously described patients suffering from leukoencephalopathy caused by AARS2 mutations. We have documented a new, nonsense AARS2 gene mutation (c.578T>G, p.Leu193*) and a known missense mutation (c.595C>T, p.Arg199Cys) associated with leukoencephalopathy in a male patient. Clinical features, imaging characteristics and genetic testing are presented, and histological data from an AARS2-related leukodystrophy patient are described for the first time.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Alanine-tRNA Ligase / genetics*
  • Cognition Disorders / genetics
  • Female
  • Genetic Testing
  • Humans
  • Leukoencephalopathies / diagnosis*
  • Leukoencephalopathies / genetics*
  • Leukoencephalopathies / pathology
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense / genetics*
  • Phenotype
  • Primary Ovarian Insufficiency / genetics
  • White Matter / abnormalities*


  • Aarsd1 protein, human
  • Alanine-tRNA Ligase