Your browser doesn't support javascript.
loading
A previously unreported NARS1 variant causes dominant distal hereditary motor neuropathy in a French family.
Theuriet, Julian; Marte, Sheila; Isapof, Arnaud; de Becdelièvre, Alix; Konyukh, Marina; Laureano-Figueroa, Stephanie M; Latour, Philippe; Quadrio, Isabelle; Maisonobe, Thierry; Antonellis, Anthony; Stojkovic, Tanya.
Afiliación
  • Theuriet J; Service 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.
  • Marte S; Pathophysiology and Genetics of Neuron and Muscle, CNRS UMR 5261, INSERM U1315, Université Lyon 1, Faculté de Médecine Lyon Est, Lyon, France.
  • Isapof A; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • de Becdelièvre A; Service de Neurologie Pédiatrique, Hôpital Trousseau, Assistance Publique des Hôpitaux de Paris, Paris, France.
  • Konyukh M; Département de Génétique Médicale, Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
  • Laureano-Figueroa SM; Laboratoire de biologie médicale multisites SeqOIA - PFMG2025, Paris, France.
  • Latour P; Département de Génétique Médicale, Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France.
  • Quadrio I; Laboratoire de biologie médicale multisites SeqOIA - PFMG2025, Paris, France.
  • Maisonobe T; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
  • Antonellis A; Service de Biochimie et Biologie Moléculaire, Unité fonctionnelle des pathologies neurologiques héréditaires, Hospices Civils de Lyon, Groupement Est, Bron, France.
  • Stojkovic T; Service de Biochimie et Biologie Moléculaire, Unité fonctionnelle des pathologies neurologiques héréditaires, Hospices Civils de Lyon, Groupement Est, Bron, France.
J Peripher Nerv Syst ; 29(2): 275-278, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38769024
ABSTRACT
BACKGROUND AND

AIMS:

Pathogenic 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.

METHODS:

The 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.

RESULTS:

The 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.

INTERPRETATION:

Our 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.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropatía Hereditaria Motora y Sensorial / Aminoacil-ARNt Sintetasas Límite: Adult / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: J Peripher Nerv Syst Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropatía Hereditaria Motora y Sensorial / Aminoacil-ARNt Sintetasas Límite: Adult / Female / Humans / Male / Middle aged País/Región como asunto: Europa Idioma: En Revista: J Peripher Nerv Syst Asunto de la revista: NEUROLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos