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Peripheral neuropathy and cognitive impairment associated with a novel monoallelic; HARS; variant

Royer-Bertrand, Béryl and Tsouni, Pinelopi and Mullen, Patrick and Campos Xavier, Belinda and Mittaz Crettol, Lauréane and Lobrinus, Alexander J. and Ghika, Joseph and Baumgartner, Matthias R. and Rivolta, Carlo and Superti-Furga, Andrea and Kuntzer, Thierry and Francklyn, Christopher and Tran, Christel. (2019) Peripheral neuropathy and cognitive impairment associated with a novel monoallelic; HARS; variant. Annals of clinical and translational neurology, 6 (6). pp. 1072-1080.

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Abstract

A 49-year-old male presented with late-onset demyelinating peripheral neuropathy, cerebellar atrophy, and cognitive deficit. Nerve biopsy revealed intra-axonal inclusions suggestive of polyglucosan bodies, raising the suspicion of adult polyglucosan bodies disease (OMIM 263570).; While known genes associated with polyglucosan bodies storage were negative, whole-exome sequencing identified an unreported monoallelic variant, c.397G>T (p.Val133Phe), in the histidyl-tRNA synthetase (; HARS; ) gene. While we did not identify mutations in genes known to be associated with polygucosan body disease, whole-exome sequencing revealed an unreported monoallelic variant, c.397G>T in the histidyl-tRNA synthetase (HARS) gene, encoding a substitution (Val133Phe) in the catalytic domain. Expression of this variant in patient cells resulted in reduced aminoacylation activity in extracts obtained from dermal fibroblasts, without compromising overall protein synthesis.; Genetic variants in the genes coding for the different aminoacyl-tRNA synthases are associated with various clinical conditions. To date, a number of HARS variant have been associated with peripheral neuropathy, but not cognitive deficits. Further studies are needed to explore why HARS mutations confer a neuronal-specific phenotype.
Faculties and Departments:09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB)
09 Associated Institutions > Institute of Molecular and Clinical Ophthalmology Basel (IOB) > Research Group Rivolta IOB
UniBasel Contributors:Rivolta, Carlo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Wiley
ISSN:2328-9503
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:26 Feb 2021 11:27
Deposited On:26 Feb 2021 11:27

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