Alanyl-tRNA Synthetase 2 (AARS2)-Related Ataxia Without Leukoencephalopathy

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 c...

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Bibliographic Details
Published in:Cerebellum (London, England) England), 2020-02, Vol.19 (1), p.154-160
Main Authors: Kuo, Molly E., Antonellis, Anthony, Shakkottai, Vikram G.
Format: Article
Language:English
Subjects:
Adult
Alanine-tRNA ligase
Alanine-tRNA Ligase - genetics
Amino Acid Sequence
Ataxia
Ataxia - diagnostic imaging
Ataxia - genetics
Biomedical and Life Sciences
Biomedicine
Cerebellar ataxia
Cerebellum
Cognitive ability
Complementation
Female
Humans
Leukoencephalopathies - diagnostic imaging
Leukoencephalopathies - genetics
Leukoencephalopathy
Magnetic resonance imaging
Male
Mitochondria
Neurobiology
Neurology
Neurosciences
Pedigree
Reproductive status
Short Reports
Siblings
tRNA
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Summary: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.
ISSN:1473-4222
1473-4230
DOI:10.1007/s12311-019-01080-y