Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability

Angebault Claire, Charif Majida, Guegen Naig, Piro-Megy Camille, Mousson de Camaret Camille, Procaccio Vincent, Guichet Pierre-Olivier, Hebrard Maxime, Manes Gael, Leboucq Nicolas, Rivier François, Hamel Christian P., Lenaers Guy, Roubertie Agathe. 2015. Mutation in NDUFA13/GRIM19 leads to early onset hypotonia, dyskinesia and sensorial deficiencies, and mitochondrial complex I instability. Human Molecular Genetics, 24 (14) : 3948-3955.

Url - jeu de données - Entrepôt autre : http://www.ncbi.nlm.nih.gov/clinvar/?term=SCV000153676

Quartile : Q1, Sujet : GENETICS & HEREDITY / Quartile : Q1, Sujet : BIOCHEMISTRY & MOLECULAR BIOLOGY

Résumé : Mitochondrial complex I (CI) deficiencies are causing debilitating neurological diseases, among which, the Leber Hereditary Optic Neuropathy and Leigh Syndrome are the most frequent. Here, we describe the first germinal pathogenic mutation in the NDUFA13/GRIM19 gene encoding a CI subunit, in two sisters with early onset hypotonia, dyskinesia and sensorial deficiencies, including a severe optic neuropathy. Biochemical analysis revealed a drastic decrease in CI enzymatic activity in patient muscle biopsies, and reduction of CI-driven respiration in fibroblasts, while the activities of complex II, III and IV were hardly affected. Western blots disclosed that the abundances of NDUFA13 protein, CI holoenzyme and super complexes were drastically reduced in mitochondrial fractions, a situation that was reproduced by silencing NDUFA13 in control cells. Thus, we established here a correlation between the first mutation yet identified in the NDUFA13 gene, which induces CI instability and a severe but slowly evolving clinical presentation affecting the central nervous system.

Mots-clés Agrovoc : activité enzymatique, névropathie, mutation, transmission des maladies, fibroblaste, génome, séquence nucléotidique

Agences de financement hors UE : Agence Nationale de la Recherche, Genzyme, Retina France, Union Nationale des Aveugles et Déficients Visuels

Auteurs et affiliations

• Angebault Claire, Université de Montpellier (FRA)
• Charif Majida, Université de Montpellier (FRA)
• Guegen Naig, CHU Angers (FRA)
• Piro-Megy Camille, CHU Angers (FRA) ORCID: 0009-0007-1275-2612
• Mousson de Camaret Camille, Université de Montpellier (FRA)
• Procaccio Vincent, CHU Angers (FRA)
• Guichet Pierre-Olivier, Université de Montpellier (FRA)
• Hebrard Maxime, Université de Montpellier (FRA)
• Manes Gael, Université de Montpellier (FRA)
• Leboucq Nicolas, CHU Montpellier (FRA)
• Rivier François, CHU Montpellier (FRA)
• Hamel Christian P., Université de Montpellier (FRA)
• Lenaers Guy, Université de Montpellier (FRA)
• Roubertie Agathe, Université de Montpellier (FRA) - auteur correspondant

Source : Cirad-Agritrop (https://agritrop.cirad.fr/611323/)

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