Evidence map›Paper›PMID 38769024›Full record

ArticleJournal of the peripheral nervous system : JPNS2024

A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family.

Julian Theuriet, Sheila Marte, Arnaud Isapof, Alix de Becdelièvre, Marina Konyukh, Stephanie M Laureano-Figueroa, Philippe Latour, Isabelle Quadrio, Thierry Maisonobe, Anthony Antonellis and 1 more

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Article in Journal of the peripheral nervous system : JPNS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Julian TheurietService d'ENMG et de pathologies neuromusculaires, centre de référence des maladies neuromusculaires PACA-Réunion-Rhône-Alpes, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Groupement Est, Bron, France.
Sheila MarteDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Arnaud IsapofService de Neurologie Pédiatrique, Hôpital Trousseau, Assistance Publique des Hôpitaux de Paris, Paris, France.
Alix de BecdelièvreDépartement de Génétique Médicale, Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Marina KonyukhDépartement de Génétique Médicale, Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Stephanie M Laureano-FigueroaDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Philippe LatourService de Biochimie et Biologie Moléculaire, Unité fonctionnelle des pathologies neurologiques héréditaires, Hospices Civils de Lyon, Groupement Est, Bron, France.
Isabelle QuadrioService de Biochimie et Biologie Moléculaire, Unité fonctionnelle des pathologies neurologiques héréditaires, Hospices Civils de Lyon, Groupement Est, Bron, France.
Thierry MaisonobeDépartement de Neurophysiologie Clinique, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France.
Anthony AntonellisDepartment of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Tanya StojkovicCentre de référence des Maladies Neuromusculaires Nord/Est/Ile de France, Institut de Myologie, Hôpital Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris, Paris, France.ORCID 0000-0002-4054-2838

Funding

MICHIGAN MEDICAL SCIENTIST TRAINING PROGRAMT32GM007863 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI COLLINS, KATHLEEN L. · 1985 to 2024
$38.3M
PREDOCTORAL TRAINING IN GENETICST32GM007544 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MORAN, JOHN V. · 1985 to 2022
$11.3M
Defining the Role of Aminoacyl-tRNA Synthetases in Human Health and DiseaseR35GM136441 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Anthony Antonellis · 2020 to 2026
$2.8M
Michigan Pre-doctoral Training Program in Genetics GM007544NIGMS NIH HHS GM136441NIGMS NIH HHS R35 GM136441NIGMS NIH HHS T32 GM007544NIGMS NIH HHS T32 GM007863
6 · The paper itself

Abstract

BACKGROUND AND

aimsPathogenic variants in the NARS1 gene, which encodes for the asparaginyl-tRNA synthetase1 (NARS1) enzyme, were associated with complex central and peripheral nervous system phenotypes. Recently, Charcot-Marie-Tooth (CMT) disease has been linked to heterozygous pathogenic variants in NARS1 in nine patients. Here, we report two brothers and their mother from a French family with distal hereditary motor neuropathy (dHMN) carrying a previously unreported NARS1 variant.

methodsThe NARS1 variant (c.1555G>C; p.(Gly519Arg)) was identified through whole-genome sequencing (WGS) performed on the family members. Clinical findings, nerve conduction studies (NCS), needle electromyography (EMG), and functional assays in yeast complementation assays are reported here.

resultsThe family members showed symptoms of dHMN, including distal weakness and osteoarticular deformities. They also exhibited brisk reflexes suggestive of upper motor neuron involvement. All patients were able to walk independently at the last follow-up. NCS and EMG confirmed pure motor neuropathy. Functional assays in yeast confirmed a loss-of-function effect of the variant on NARS1 activity.

interpretationOur findings expand the clinical spectrum of NARS1-associated neuropathies, highlighting the association of NARS1 mutations with dHMN. The benign disease course observed in our patients suggests a slowly progressive phenotype. Further reports could contribute to a more comprehensive understanding of the spectrum of NARS1-associated neuropathies.

Indexed as

Amino Acyl-tRNA SynthetasesHereditary Sensory and Motor NeuropathyAdultAspartate-tRNA LigaseCharcot-Marie-Tooth DiseaseFemaleFranceHumansMaleMiddle AgedPedigreeRNA, Transfer, Amino AcylAmino Acyl-tRNA Synthetasesasparaginyl-tRNA synthetaseAspartate-tRNA LigaseRNA, Transfer, Amino Acylasparaginyl‐tRNA synthetaseCharcot–Marie–Tooth diseasedistal hereditary motor neuropathyNARS1

Identifiers

PMID38769024
PMCPMC11414471

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.