Alanyl-tRNA synthetase 1 gene variants in hereditary neuropathy genotype and phenotype overview
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Date
2022-10-05
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Abstract
Background and Objectives Our objective was to report 2 novel variants and to reclassify previously reported alanyl-tRNA synthetase 1 (AARS1) variants associated with hereditary neuropathy and to summarize the clinical features of a previously published cohort of patients. Methods We performed detailed neurologic and electrophysiologic assessments and segregation analysis of 2 unrelated families with Charcot-Marie-Tooth (CMT) disease with novel variants in the AARS1 gene. Via literature search, we found studies that included neuropathy cases with AARS1 variants; we then reviewed and reclassified these variants. Results We identified 2 CMT families harboring previously unreported likely pathogenic AARS1 variants: c.1823C>A p.(Thr608Lys) and c.1815C>G p.(His605Gln). In addition, we reinterpreted a total of 35 different AARS1 variants reported in cases with neuropathy from the literature: 9 variants fulfilled the current criteria for being (likely) pathogenic. We compiled and summarized standardized clinical and genotypic information for 90 affected individuals from 32 families with (likely) pathogenic AARS1 variants. Most experienced motor weakness and sensory loss in the lower limbs. Discussion In total, 11 AARS1 variants can currently be classified as pathogenic or likely pathogenic and are associated with sensorimotor axonal or intermediate, slowly progressive polyneuropathy with common asymmetry and variable age of symptom onset with no apparent involvement of other organ systems.
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Funding Information: This research is funded by Latvian Science Council, Project Discovering biomarkers of disease progression and variability in Charcot-Marie-Tooth neuropathy, No lzp-2021/1-0327. Funding Information: The Article Processing Charge was funded by Fundamental and Applied Research Project, lzp-2021/1-0327. Publisher Copyright: Copyright © 2022 The Author(s).
Keywords
3.2 Clinical medicine, 3.1 Basic medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, Clinical Neurology, Genetics(clinical)
Citation
Setlere, S, Jurcenko, M, Gailite, L, Rots, D & Kenina, V 2022, 'Alanyl-tRNA synthetase 1 gene variants in hereditary neuropathy genotype and phenotype overview', Neurology: Genetics, vol. 8, no. 5, e200019. https://doi.org/10.1212/NXG.0000000000200019