Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus​

Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus

Our research interests focus on two groups of neuromuscular disorders (NMD): myopathies due to abnormalities of the myomatrix and of the nucleus. The long-term objective of our work is to propose relevant therapeutic options based on our knowledge of the genetic basis and of the underlying pathomechanisms at play in these rare diseases.

Research Project: Genetics and pathophysiology of neuromuscular disorders linked to the extracellular matrix and to the nucleus

Our team focuses on 2 groups of neuromuscular disorders: myopathies due to the defective myomatrix (collagen VI and other components of the extracellular matrix) and to defects of the myonucleus (Emery-Dreifuss muscular dystrophy and other striated muscle laminopathies due to mutations in the laminA/C gene or genes encoding components of nuclear membrane). These myopathies share some clinical features, notably prominent contractures, and constitute differential diagnosis[in1] .

These disorders are highly heterogeneous, clinically and genetically, and to date no treatment is available. Our previous work led us to identify the involvement of various genetic alterations and to develop tools (cellular and animal models) that are crucial for deciphering pathomechanisms, understanding the molecular defects and unveiling therapeutic targets.

We are still facing several challenges and bottlenecks: 1) a number of patients are still awaiting molecular diagnosis; 2) relevant biomarkers are scarce; 3) functions of the involved proteins and underlying pathomechanisms are still poorly understood … We previously have and continue to tackle several transverse processes (e.g. contractile dysfunction, defective mechanosensing, fibrosis …) using our specific expertise (nuclear envelop, nucleoplasm, extracellular matrix…).

Current research axes:

  • Definition of genetic and clinical spectrum and delineation of natural history of these NMDs,
  • Development of new tools to validate genetic variants identified through NGS (next generation sequencing),
  • Deciphering pathomechanisms that affect skeletal and/or cardiac muscle, with the overall goal of identifying and assessing therapeutic options for these disorders.

Our work is carried out on biological material derived from patients (DNA, RNA cultured cells, or muscle biopsies), and on animal models developed in the team (mouse, zebrafish).

Noyau-MEC ©Astrid Brull

Noyau-MEC ©Astrid Brull

Equipe BONNE
Gisèle Bonne


Gisèle Bonne


336 documents

  • Gisèle Bonne. Présentation des actions Recherche de la Filière en Santé Maladies Rares Neuromusculaires - FILNEMUS. 2023. ⟨hal-04000635⟩
  • Rocio García-Uzquiano, Marta Gómez-García de la Banda, Laure Le Goff, Véronique Manel, Ivana Dabaj, et al.. Expérience de l’utilisation des corticoïdes dans les laminopathies de l’enfant. 32 ème congrès de la Société Française de Neurologie Pédiatrique, Marseille, Jan 2023, Marseille (FRANCE), France. ⟨hal-04015316⟩
  • Louise Benarroch, Gisèle Bonne, François Rivier, Dalil Hamroun. The 2023 version of the gene table of neuromuscular disorders (nuclear genome). Neuromuscular Disorders, 2023, 33 (1), pp.76-117. ⟨10.1016/j.nmd.2022.12.002⟩. ⟨hal-03964998⟩
  • Ana Rita Carlos, Valérie Allamand. Editorial: Extracellular matrix in homeostasis and cancer. Frontiers in Genetics, 13, 2022, Extracellular matrix in homeostasis and cancer, ⟨10.3389/fgene.2022.1107969⟩. ⟨hal-03968194⟩
  • Clémence Labasse, Guy Brochier, Ana-Lia Taratuto, Bruno CADOT, John Rendu, et al.. Severe ACTA1-related nemaline myopathy: intranuclear rods, cytoplasmic bodies, and enlarged perinuclear space as characteristic pathological features on muscle biopsies. Acta Neuropathologica Communications, 2022, 10 (1), pp.101. ⟨10.1186/s40478-022-01400-0⟩. ⟨hal-03820052⟩
  • Tanya Stojkovic, Marion Masingue, Helène Turmel, Marianne Hezode-Arzel, Anthony Béhin, et al.. Diagnostic yield of a practical electrodiagnostic protocol discriminating between different congenital myasthenic syndromes. Neuromuscular Disorders, 2022, 32 (11-12), pp.870-878. ⟨10.1016/j.nmd.2022.10.001⟩. ⟨hal-03993811⟩
  • Valérie Allamand. Vers une meilleure détection des variants introniques et autres anomalies d’épissage complexes dans les dystrophinopathies. 2022, pp.39-39. ⟨10.1051/medsci/2022182⟩. ⟨hal-03968248⟩
  • Gisèle Bonne. Table Ronde: Quel avenir pour la recherche sur les maladies rares ?. Dix ans de contribution de l’ANR au domaine des maladies rares, Nov 2022, Paris, France. ⟨hal-03984507⟩
  • Marine Leconte, Gisèle Bonne, Anne T Bertrand. Etude des dommages de l'ADN dans la dystrophie musculaire congénitale liée à LMNA. 19èmes Journées de la Société Française de Myologie, Nov 2022, Toulouse, France. ⟨hal-04004845⟩
  • Aurélien Perrin, Charles Van Goethem, Corinne Métay, Raul Juntas Morales, Françoise Chapon, et al.. Analyses fonctionnelles et études de corrélation phénotype-génotype chez des patients suspects de titinopathie. 19èmes Journées de la Société Française de Myologie, Nov 2022, Toulouse, France. ⟨hal-04004837⟩
AFM Telethon : innover pour guérir
Agence nationale de la recherche
Congenital Muscular Dystrophy Research
Muscular Dystrophy UK - Fighting Muscle-wasting conditions
Solving the Unsolved Rare Diseases
European Research Area Network on Cardiovascular Diseases

Our last work on the OJRD

A guide to writing systematic reviews of rare disease treatments to generate FAIRcompliant datasets: building a Treatabolome

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