Expansion of the clinical spectrum associated with AARS2-related disorders

Siddharth Srivastava, Ankur Butala, Sonal Mahida, John Richter, Weiyi Mu, Andrea Poretti, Hilary J Vernon, Jay VanGerpen, Paldeep S. Atwal, Erik H. Middlebrooks, David Samuel Zee, Sakkubai Naidu

Research output: Contribution to journalArticle

Abstract

Biallelic pathogenic variants in AARS2, a gene encoding the mitochondrial alanyl-tRNA synthetase, result in a spectrum of findings ranging from infantile cardiomyopathy to adult-onset progressive leukoencephalopathy. In this article, we present three unrelated individuals with novel compound heterozygous pathogenic AARS2 variants underlying diverse clinical presentations. Patient 1 is a 51-year-old man with adult-onset progressive cognitive, psychiatric, and motor decline and leukodystrophy. Patient 2 is a 34-year-old man with childhood-onset progressive tremor followed by the development of polyneuropathy, ataxia, and mild cognitive and psychiatric decline without leukodystrophy on imaging. Patient 3 is a 57-year-old woman with childhood-onset tremor and nystagmus which preceded dystonia, chorea, ataxia, depression, and cognitive decline marked by cerebellar atrophy and white matter disease. These cases expand the clinical heterogeneity of AARS2-related disorders, given that the first and third case represent some of the oldest known survivors of this disease, the second is adult-onset AARS2-related neurological decline without leukodystrophy, and the third is biallelic AARS2-related disorder involving a partial gene deletion.

Original languageEnglish (US)
JournalAmerican Journal of Medical Genetics, Part A
DOIs
StatePublished - Jan 1 2019

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Leukoencephalopathies
Tremor
Ataxia
Psychiatry
Alanine-tRNA Ligase
Chorea
Mitochondrial Genes
Dystonia
Polyneuropathies
Gene Deletion
Cardiomyopathies
Atrophy
Survivors
Depression
Cognitive Dysfunction
White Matter

Keywords

  • AARS2
  • leukodystrophy
  • movement disorder
  • polyneuropathy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Expansion of the clinical spectrum associated with AARS2-related disorders. / Srivastava, Siddharth; Butala, Ankur; Mahida, Sonal; Richter, John; Mu, Weiyi; Poretti, Andrea; Vernon, Hilary J; VanGerpen, Jay; Atwal, Paldeep S.; Middlebrooks, Erik H.; Zee, David Samuel; Naidu, Sakkubai.

In: American Journal of Medical Genetics, Part A, 01.01.2019.

Research output: Contribution to journalArticle

Srivastava, Siddharth ; Butala, Ankur ; Mahida, Sonal ; Richter, John ; Mu, Weiyi ; Poretti, Andrea ; Vernon, Hilary J ; VanGerpen, Jay ; Atwal, Paldeep S. ; Middlebrooks, Erik H. ; Zee, David Samuel ; Naidu, Sakkubai. / Expansion of the clinical spectrum associated with AARS2-related disorders. In: American Journal of Medical Genetics, Part A. 2019.
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