Novel AARS2 gene mutation producing leukodystrophy: a case report.

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Mutations in the AARS2 gene are associated with distinct phenotypes, including infantile mitochondrial cardiomyopathy and late-onset leukoencephalopathy.
• Leukoencephalopathy is a group of rare neurological disorders characterized by abnormalities in the brain's white matter.

Observation:

• A male patient presented at 18 years old with behavioral changes, psychiatric issues, and later developed extrapyramidal and pyramidal symptoms, cognitive impairment, nystagmus, and dysarthria.
• Brain MRI revealed extensive white matter abnormalities, consistent with leukodystrophy.
• Genetic testing confirmed compound heterozygous mutations in the AARS2 gene.

Findings:

• A novel nonsense mutation (c.578T>G, p.Leu193*) and a known missense mutation (c.595C>T, p.Arg199Cys) in the AARS2 gene were identified in the patient.
• Histological examination of a biopsy did not reveal specific pathological alterations, representing the first histological data described for AARS2-related leukodystrophy.
• The patient's clinical phenotype aligns with previously reported cases of AARS2-associated leukoencephalopathy.

Implications:

• This study expands the mutational spectrum of AARS2-related leukoencephalopathy and provides novel insights into its histopathology.
• Understanding the genetic basis and clinical spectrum of AARS2 mutations is crucial for accurate diagnosis and potential therapeutic strategies.
• Further research is warranted to elucidate the precise molecular mechanisms underlying AARS2-related leukoencephalopathy.