Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy
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Mutations in the mitochondrial alanyl-tRNA synthetase gene, AARS2, have been reported to cause leukoencephalopathy associated with early ovarian failure, a clinical presentation described as “ovarioleukodystrophy.” We present a sibling pair: one with cerebellar ataxia and one with vision loss and cognitive impairment in addition to ataxia. Neither shows evidence of leukoencephalopathy on MRI imaging. Exome sequencing revealed that both siblings are compound heterozygous for AARS2 variants (p.Phe131del and p.Ile328Met). Yeast complementation assays indicate that p.Phe131del AARS2 dramatically impairs gene function and that p.Ile328Met AARS2 is a hypomorphic allele. This work expands the phenotypic spectrum of AARS2-associated disease to include ataxia without leukoencephalopathy.
KeywordsAARS2 Cerebellar ataxia Ovarioleukodystrophy Leukoencephalopathy Recessive ataxia
M.E.K. is supported by the NIH Medical Scientist Training Program Training Grant (GM007863), the NIH Cellular and Molecular Biology Training Grant (GM007315), and an NIH National Research Service Award (F31) from the National Institute of Neurological Disorders and Stroke (NS113515). A.A. is supported by a grant from the National Institute of General Medical Sciences (GM118647). V.G.S is supported by a grant from the NINDS (NS085054).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflicts of interest.
Informed consent was obtained from all individual participants included in the study.
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