Phenotype-specific muscle proteomic profiling in titinopathies
Abstract
Titinopathies are complex neuromuscular disorders with multiple phenotypes. The gene's size, comprising 364 exons, as well as the protein's size of 3.8 MDa and its extensive network of protein interactors, are key factors underlying this complexity. Various phenotypes characterize titinopathies, and this study focuses on two of them: arthrogryposis and myofibrillar myopathies. The protein deregulations associated with these two phenotypes remain unknown or have been minimally explored; however, understanding these consequences is essential for better characterizing the pathophysiological aspects of these titinopathies.The objective was to analyze protein deregulations in two cohorts of French patients with titinopathies exhibiting the arthrogryposis and myofibrillar myopathy phenotypes, and to compare them with control individuals. Protein extracts were obtained from muscle biopsies of patients, and changes in protein levels within these two groups were analyzed by mass spectrometry. The results indicate specific deregulations in each group. The networks analyzed revealed deregulation of proteins involved in fibrosis mechanisms or in the actomyosin complex for the arthrogryposis phenotype. Regulation of the muscle contraction system through deregulation of proteins involved in the cytoskeleton is impacted in patients with myofibrillar myopathy. The proteins that are quantitatively abnormal in these two groups also provide insights into the major signaling networks disrupted in titinopathies. These findings will contribute to a more precise characterization of titinopathies, enabling the identification of phenotype-specific biomarkers and potentially guiding the search for targeted therapies for these neuromuscular disorders.
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BibTeX
@article{perrin2026phenotypespecific,
title = {{Phenotype-specific muscle proteomic profiling in titinopathies}},
author = {Aurélien Perrin and Marie-Rocio Casenave-Camgaston and Baptiste Rabillard and Fabrice Raynaud and Serge Urbach and Martial Seveno and Ana Maria Navarro and Anas Tendero-Baziou and Stephan Matecki and Claude Cancès and Julien Durigneux and Valérie Biancalana and Florence Petit and Céline Tard and Arnaud Molin and Manon Godin and Xénia Latypova and John Rendu and Médéric Jeanne and Raul Juntas Morales and Emmanuelle Salort-Campana and Annie Verschueren and Martin Krahn and Svetlana Gorokhova and Shahram Attarian and Guilhem Solé and Florence Esselin and Marie-Laure Martin-Négrier and Corinne Métay and Christian Jorgensen and Anne Bergougnoux and Michel Koenig and Mireille Cossée},
journal = {Acta Neuropathologica Communications},
year = {2026},
month = jul,
doi = {10.1186/s40478-026-02363-2},
url = {https://hal.science/hal-05679641v2},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Phenotype-specific muscle proteomic profiling in titinopathies
AU - Aurélien Perrin
AU - Marie-Rocio Casenave-Camgaston
AU - Baptiste Rabillard
AU - Fabrice Raynaud
AU - Serge Urbach
AU - Martial Seveno
AU - Ana Maria Navarro
AU - Anas Tendero-Baziou
AU - Stephan Matecki
AU - Claude Cancès
AU - Julien Durigneux
AU - Valérie Biancalana
AU - Florence Petit
AU - Céline Tard
AU - Arnaud Molin
AU - Manon Godin
AU - Xénia Latypova
AU - John Rendu
AU - Médéric Jeanne
AU - Raul Juntas Morales
AU - Emmanuelle Salort-Campana
AU - Annie Verschueren
AU - Martin Krahn
AU - Svetlana Gorokhova
AU - Shahram Attarian
AU - Guilhem Solé
AU - Florence Esselin
AU - Marie-Laure Martin-Négrier
AU - Corinne Métay
AU - Christian Jorgensen
AU - Anne Bergougnoux
AU - Michel Koenig
AU - Mireille Cossée
PY - 2026
DA - 2026/07/02
JO - Acta Neuropathologica Communications
DO - 10.1186/s40478-026-02363-2
UR - https://hal.science/hal-05679641v2
AB - Titinopathies are complex neuromuscular disorders with multiple phenotypes. The gene's size, comprising 364 exons, as well as the protein's size of 3.8 MDa and its extensive network of protein interactors, are key factors underlying this complexity. Various phenotypes characterize titinopathies, and this study focuses on two of them: arthrogryposis and myofibrillar myopathies. The protein deregulations associated with these two phenotypes remain unknown or have been minimally explored; however, understanding these consequences is essential for better characterizing the pathophysiological aspects of these titinopathies.The objective was to analyze protein deregulations in two cohorts of French patients with titinopathies exhibiting the arthrogryposis and myofibrillar myopathy phenotypes, and to compare them with control individuals. Protein extracts were obtained from muscle biopsies of patients, and changes in protein levels within these two groups were analyzed by mass spectrometry. The results indicate specific deregulations in each group. The networks analyzed revealed deregulation of proteins involved in fibrosis mechanisms or in the actomyosin complex for the arthrogryposis phenotype. Regulation of the muscle contraction system through deregulation of proteins involved in the cytoskeleton is impacted in patients with myofibrillar myopathy. The proteins that are quantitatively abnormal in these two groups also provide insights into the major signaling networks disrupted in titinopathies. These findings will contribute to a more precise characterization of titinopathies, enabling the identification of phenotype-specific biomarkers and potentially guiding the search for targeted therapies for these neuromuscular disorders.
SN - 2051-5960
ER -