Published 2024
| Version v1
Journal article
Primary mitochondrial disorders and mimics: Insights from a large French cohort
Creators
- Rouzier, Cécile
- Pion, Emmanuelle
- Chaussenot, Annabelle
- Bris, Céline
- Ait-El-Mkadem Saadi, Samira
- Desquiret-Dumas, Valérie
- Gueguen, Naïg
- Fragaki, Konstantina
- Amati-Bonneau, Patrizia
- Barcia, Giulia
- Gaignard, Pauline
- Steffann, Julie
- Pennisi, Alessandra
- Bonnefont, Jean‐paul
- Lebigot, Elise
- Bannwarth, Sylvie
- Francou, Bruno
- Rucheton, Benoit
- Sternberg, Damien
- Martin-Negrier, Marie‐laure
- Trimouille, Aurélien
- Hardy, Gaëlle
- Allouche, Stéphane
- Acquaviva-Bourdain, Cécile
- Pagan, Cécile
- Lebre, Anne‐sophie
- Reynier, Pascal
- Cossee, Mireille
- Attarian, Shahram
- Paquis-Flucklinger, Véronique
- Procaccio, Vincent
Contributors
Others:
- Institut de Recherche sur le Cancer et le Vieillissement (IRCAN) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA)
- Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
- Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)
- Hôpital Bicêtre [AP-HP, Le Kremlin-Bicêtre] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- CHU Bordeaux
- CHU Pitié-Salpêtrière [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Hôpital Pellegrin ; CHU Bordeaux-Groupe hospitalier Pellegrin
- Centre Hospitalier Universitaire [CHU Grenoble] (CHUGA)
- Hôpital Côte de Nacre [CHU Caen] ; CHU Caen ; Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)
- Groupement Hospitalier Lyon-Est (GHE) ; Hospices Civils de Lyon (HCL)
- Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)
- Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
- Hôpital de la Timone [CHU - APHM] (TIMONE)
Description
Objective: The objective of this study was to evaluate the implementation of NGS within the French mitochondrial network, MitoDiag, from targeted gene panels to whole exome sequencing (WES) or whole genome sequencing (WGS) focusing on mitochondrial nuclear‐encoded genes.Methods: Over 2000 patients suspected of Primary Mitochondrial Diseases (PMD) were sequenced by either targeted gene panels, WES or WGS within MitoDiag. We described the clinical, biochemical, and molecular data of 397 genetically confirmed patients, comprising 294 children and 103 adults, carrying pathogenic or likely pathogenic variants in nuclear‐encoded genes.Results: The cohort exhibited a large genetic heterogeneity, with the identification of 172 distinct genes and 253 novel variants. Among children, a notable prevalence of pathogenic variants in genes associated with oxidative phosphorylation (OXPHOS) functions and mitochondrial translation was observed. In adults, pathogenic variants were primarily identified in genes linked to mtDNA maintenance. Additionally, a substantial proportion of patients (54% (42/78) and 48% (13/27) in children and adults, respectively), undergoing WES or WGS testing displayed PMD mimics, representing pathologies that clinically resemble mitochondrial diseases. Interpretation We reported the largest French cohort of patients suspected of PMD with pathogenic variants in nuclear genes. We have emphasized the clinical complexity of PMD and the challenges associated with recognizing and distinguishing them from other pathologies, particularly neuromuscular disorders. We confirmed that WES/WGS, instead of panel approach, was more valuable to identify the genetic basis in patients with "possible" PMD and we provided a genetic testing flowchart to guide physicians in their diagnostic strategy.
Abstract
International audienceAdditional details
Identifiers
- URL
- https://hal.science/hal-04569049
- URN
- urn:oai:HAL:hal-04569049v1
Origin repository
- Origin repository
- UNICA