Early onset epileptic encephalopathy and deficient myelination as a result of autosomal recessive mutations in the AARS gene (S22.007)

TL;DRAbstract

OBJECTIVE Identify the underlying etiology in a series of patients with white matter abnormality on MRI and early onset epileptic encephalopathy with club foot, peripheral neuropathy and extrapyramidal features. BACKGROUND Mutations in genes encoding aminoacyl-transfer RNA (tRNA) synthetases are known to cause a growing number of leukodystrophies and genetic leukoencephalopathies (heritable disorders with white matter abnormalities on magnetic resonance imaging (MRI)). Whole exome sequencing (WES) has rapidly advanced the implication of these genes in disease. DESIGN/METHODS Patients were collected from an IRB approved repository, the Myelin Disorders Bioregistry Project. WES was performed on the basis of unsolved leukoencephalopathy. Subsequent analysis included aminoacylation assay, editing assay, and yeast complementation studies of identified variants. RESULTS We identified mutations in the alanyl-tRNA synthetase (AARS) gene in two unrelated families: one with two affected siblings

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