A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family
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| Název: | A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family |
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| Autoři: | Theuriet, Julian, Marte, Sheila, Isapof, Arnaud, de Becdelièvre, Alix, Konyukh, Marina, Laureano-Figueroa, Stephanie, Latour, Philippe, Quadrio, Isabelle, Maisonobe, Thierry, Antonellis, Anthony, Stojkovic, Tanya |
| Přispěvatelé: | HABLOT, Roxanne, Radiopharmaceutical and Neurochemical Biomarkers (CRNL-BIORAN), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie et Biologie Moléculaire Grand Est HCL, Lyon (Centre de Biologie et de Pathologie), Hospices Civils de Lyon (HCL) |
| Zdroj: | J Peripher Nerv Syst |
| Informace o vydavateli: | Wiley, 2024. |
| Rok vydání: | 2024 |
| Témata: | Adult, Male, 0301 basic medicine, MESH: Pedigree, [SDV.GEN] Life Sciences [q-bio]/Genetics, Charcot–Marie–Tooth disease, distal hereditary motor neuropathy, NARS1, Article, Amino Acyl-tRNA Synthetases, 03 medical and health sciences, MESH: Hereditary Sensory and Motor Neuropathy, Charcot-Marie-Tooth Disease, MESH: Charcot-Marie-Tooth Disease, Humans, MESH: Amino Acyl-tRNA Synthetases, [SDV.GEN]Life Sciences [q-bio]/Genetics, 0303 health sciences, MESH: Humans, MESH: Middle Aged, MESH: Adult, Middle Aged, asparaginyl‐tRNA synthetase, MESH: Male, Pedigree, 3. Good health, MESH: France, Female, France, Hereditary Sensory and Motor Neuropathy, MESH: Female |
| Popis: | 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. |
| Druh dokumentu: | Article Other literature type |
| Popis souboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1529-8027 1085-9489 |
| DOI: | 10.1111/jns.12635 |
| Přístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38769024 https://hal.science/hal-04801458v1 https://hal.science/hal-04801458v1/document https://doi.org/10.1111/jns.12635 |
| Rights: | CC BY NC URL: http://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| Přístupové číslo: | edsair.doi.dedup.....40e7a651eed7953b619264bb8043aaf2 |
| Databáze: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | 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. |
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| ISSN: | 15298027 10859489 |
| DOI: | 10.1111/jns.12635 |