Review
Biochemistry & Molecular Biology
Raquel Gomez-Oca, Belinda S. Cowling, Jocelyn Laporte
Summary: Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects caused by mutations in genes encoding proteins involved in membrane remodeling, trafficking, and excitation-contraction coupling. Animal models have confirmed shared pathological anomalies in T-tubule remodeling, organelle mispositioning, and protein homeostasis, supporting the development of common therapeutic targets for CNM forms. Promising preclinical results have led to ongoing clinical trials for CNM treatment, including gene therapy and repurposing of existing drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Valentina Maria Lionello, Christine Kretz, Evelina Edelweiss, Corinne Crucifix, Raquel Gomez-Oca, Nadia Messaddeq, Suzie Buono, Pascale Koebel, Xenia Massana Munoz, Nadege Diedhiou, Belinda S. Cowling, Marc Bitoun, Jocelyn Laporte
Summary: This study identifies BIN1 as a potential therapeutic target for dominant centronuclear myopathy linked to DNM2 mutations. By increasing BIN1 expression, muscle atrophy and histopathological features can be improved, and survival can be rescued.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Clinical Neurology
Charlotte Gineste, Alix Simon, Marie Braun, David Reiss, Jocelyn Laporte
Summary: The study shows that tamoxifen can improve muscle function and structure in mouse models of BIN1 and DNM2-related centronuclear myopathies, likely by reducing dynamin 2 levels. This suggests the potential repurposing of tamoxifen for the treatment of autosomal forms of centronuclear myopathies.
Review
Biochemistry & Molecular Biology
Kenshiro Fujise, Satoru Noguchi, Tetsuya Takeda
Summary: This review provides an overview of the functions of dynamin 2 and BIN1 in T-tubule biogenesis and discusses how their dysfunction in membrane remodelling leads to CNM pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Luca Bosco, Daniela Leone, Laura Costa Comellas, Mauro Monforte, Marika Pane, Eugenio Mercuri, Enrico Bertini, Adele D'Amico, Fabiana Fattori
Summary: This study identified a novel MTM1 gene variant in a three-month-old child with XLMTM, which affects the normal splicing process. The researchers expanded the genotypic spectrum of XLMTM and highlighted the importance of sequencing intron-exon boundaries in male patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ege Sarikaya, Nesrin Sabha, Jonathan Volpatti, Emanuela Pannia, Nika Maani, Hernan D. Gonorazky, Alper Celik, Yijng Liang, Paula Onofre-Oliveira, James J. Dowling
Summary: XLMTM is a severe monogenetic disorder of the skeletal muscle caused by mutations in the MTM1 gene. A study of Mtm1 KO mice revealed age-associated changes in gene expression, mitochondrial function, myofiber size, and key molecular markers, providing important insights into the disease pathomechanisms.
DISEASE MODELS & MECHANISMS
(2022)
Article
Cell Biology
Suzie Buono, Arnaud Monseur, Alexia Menuet, Anne Robe, Catherine Koch, Jocelyn Laporte, Leen Thielemans, Marion Depla, Belinda S. Cowling
Summary: Generating reliable preclinical data in animal models of disease is crucial for therapy development. In this study, statistical analysis and modeling were conducted to predict disease progression, which was then validated using data from a new colony of mice, demonstrating the reproducibility of disease phenotype. Furthermore, the refined phenotypic parameters were used to test the therapeutic efficacy of Dnm2 targeting, showing a significant improvement in disease progression.
DISEASE MODELS & MECHANISMS
(2022)
Article
Cardiac & Cardiovascular Systems
Harmonie Perdreau-Dahl, David B. Lipsett, Michael Frisk, Fatemeh Kermani, Cathrine R. Carlson, Andreas Brech, Xin Shen, Anna Bergan-Dahl, Yufeng Hou, Tomi Tuomainen, Pasi Tavi, Peter P. Jones, Marianne Lunde, J. Andrew Wasserstrom, Jocelyn Laporte, Nina D. Ullrich, Geir Christensen, J. Preben Morth, William E. Louch
Summary: This study reveals the collaborative roles of BIN1, MTM1, and DNM2 in controlling t-tubule growth in cardiomyocytes, which is crucial for the maturation of cardiomyocyte Ca2+ homeostasis.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Polina Chausova, Aysylu Murtazina, Anna Stepanova, Artem Borovicov, Valeriia Kovalskaia, Nina Ryadninskaya, Alena Chukhrova, Oxana Ryzhkova, Aleksander Poliakov
Summary: This study presents a case of X-linked centronuclear myopathy in a female carrier with a pathogenic c.1261-10A>G variant in the MTM1 gene.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pediatrics
Andreia Carvalho, Carmen Costa, Miguel Pinto, Ricardo Taipa, Ana Goncalves, Marcia E. Oliveira, Sofia Ferreira, Joana Afonso Ribeiro
Summary: We describe a case of mild XLMTM phenotype with independent gait and no respiratory insufficiency in the neonatal period. The patient carries a novel pathogenic variant in the MTM1 gene, confirmed by genetic testing and muscle biopsy findings. Comparison with similar cases suggests that residual expression of the normal myotubularin transcript may underlie this phenotype.
JOURNAL OF PEDIATRIC GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Catarina Perdigao, Mariana A. Barata, Tatiana Burrinha, Claudia Guimas Almeida
Summary: Genetic studies have identified two coding variants in the BIN1 gene associated with late-onset Alzheimer's disease risk. These variants may lead to a loss of function in endocytic recycling, impacting intracellular beta-amyloid accumulation and early endosome enlargement, potentially contributing to the pathogenesis of LOAD.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Clinical Neurology
Sietse Bouma, Nicolle Cobben, Karlijn Bouman, Michael Gaytant, Ries van de Biggelaar, Jeroen van Doorn, Stacha F. I. Reumers, Nicoline B. M. Voet, Jonne Doorduin, Corrie E. Erasmus, Erik-Jan Kamsteeg, Heinz Jungbluth, Peter Wijkstra, Nicol C. Voermans
Summary: Centronuclear myopathy (CNM) is a group of muscle disorders characterized by muscle weakness and respiratory dysfunction caused by mutations in specific genes. This study collected respiratory function data from Dutch CNM patients and found that 54% of patients had respiratory dysfunction. The study provides a basis for future natural history studies.
NEUROMUSCULAR DISORDERS
(2023)
Article
Cell & Tissue Engineering
Liani G. Devito, Valentina M. Lionello, Francesco Muntoni, Francesco Saverio Tedesco, Lyn Healy
Summary: Centronuclear myopathies (CNMs) are rare inherited muscle disorders with abnormal position of the nucleus in muscle fibers. X-Linked Myotubular Myopathy (XLMTM) is a type of CNM caused by mutations in the MTM1 gene, leading to severe muscle hypotonia and weakness, as well as bulbar and respiratory involvement. In this study, an iPSC line derived from a severe XLMTM patient was generated, providing a valuable model for disease study and therapy development.
STEM CELL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Paula Samso, Philipp A. Koch, York Posor, Wen-Ting Lo, Hassane Belabed, Marc Nazare, Jocelyn Laporte, Volker Haucke
Summary: X-linked centronuclear myopathy (XLCNM) is a severe human disease without existing therapies. This study shows that defective focal adhesions and reduced active beta-integrin surface levels in XLCNM can be rescued by loss of PI3KC2 beta function. The researchers also demonstrate the unknown role of PI3KC2 beta in the endocytic trafficking of active beta 1-integrins, providing a potential treatment option for XLCNM patients.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Genetics & Heredity
Adele D'Amico, Antonella Longo, Fabiana Fattori, Michele Tosi, Luca Bosco, Maria Beatrice Chiarini Testa, Giovanna Paglietti, Claudio Cherchi, Adelina Carlesi, Irene Mizzoni, Enrico Bertini
Summary: X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy caused by pathogenic variants in the MTM1 gene. Male patients typically present with severe symptoms at birth, requiring intensive care, and long-term survivors often depend on ventilators and feeding tubes, with possible additional organ involvement. Various therapeutic strategies are being investigated for XLMTM.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Cell Biology
Manuela D'Alessandro, Karim Hnia, Vincent Gache, Catherine Koch, Christos Gavriilidis, David Rodriguez, Anne-Sophie Nicot, Norma B. Romero, Yannick Schwab, Edgar Gomes, Michel Labouesse, Jocelyn Laporte
DEVELOPMENTAL CELL
(2015)
Article
Cell Biology
Caroline Ramspacher, Emily Steed, Francesco Boselli, Rita Ferreira, Nathalie Faggianelli, Stephane Roth, Coralie Spiegelhalter, Nadia Messaddeq, Le Trinh, Michael Liebling, Nikhil Chacko, Federico Tessadori, Jeroen Bakkers, Jocelyn Laporte, Karim Hnia, Julien Vermot
Correction
Multidisciplinary Sciences
Nassim Dali-Youcef, Karim Hnia, Sebastien Blaise, Nadia Messaddeq, Stephane Blanc, Catherine Postic, Philippe Valet, Catherine Tomasetto, Marie-Christine Rio
SCIENTIFIC REPORTS
(2016)
Article
Cell Biology
Christos Gavriilidis, Leila Laredj, Romain Solinhac, Nadia Messaddeq, Julien Viaud, Jocelyn Laporte, Izabela Sumara, Karim Hnia
NATURE CELL BIOLOGY
(2018)
Review
Cell Biology
Karim Hnia, Caroline Ramspacher, Julien Vermot, Jocelyn Laporte
CELL AND TISSUE RESEARCH
(2015)
Article
Neurosciences
M. Assoum, M. A. Salih, N. Drouot, K. Hnia, A. Martelli, M. Koenig
Article
Medicine, Research & Experimental
Sestina Falcone, William Roman, Karim Hnia, Vincent Gache, Nathalie Didier, Jeanne Laine, Frederic Aurade, Isabelle Marty, Ichizo Nishino, Nicolas Charlet-Berguerand, Norma Beatriz Romero, Giovanna Marazzi, David Sassoon, Jocelyn Laporte, Edgar R. Gomes
EMBO MOLECULAR MEDICINE
(2014)
Article
Cell Biology
Leonela Amoasii, Karim Hnia, Gaetan Chicanne, Andreas Brech, Belinda S. Cowling, Martin Michael Mueller, Yannick Schwab, Pascale Koebel, Arnaud Ferry, Bernard Payrastre, Jocelyn Laporte
JOURNAL OF CELL SCIENCE
(2013)
Review
Biochemistry & Molecular Biology
Karim Hnia, Ilaria Vaccari, Alessandra Bolino, Jocelyn Laporte
TRENDS IN MOLECULAR MEDICINE
(2012)
Article
Multidisciplinary Sciences
Laura Picas, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurelien Roux, Patricia Bassereau, Frederique Gaits-Iacovoni, Bernard Payrastre, Jocelyn Laporte, Jean-Baptiste Manneville, Bruno Goud
NATURE COMMUNICATIONS
(2014)
Article
Multidisciplinary Sciences
Nassim Dali-Youcef, Karim Hnia, Sebastien Blaise, Nadia Messaddeq, Stephane Blanc, Catherine Postic, Philippe Valet, Catherine Tomasetto, Marie-Christine Rio
SCIENTIFIC REPORTS
(2016)
Article
Genetics & Heredity
Leonela Amoasii, Dimitri L. Bertazzi, Helene Tronchere, Karim Hnia, Gaetan Chicanne, Bruno Rinaldi, Belinda S. Cowling, Arnaud Ferry, Bruno Klaholz, Bernard Payrastre, Jocelyn Laporte, Sylvie Friant
Article
Genetics & Heredity
Vandana A. Gupta, Karim Hnia, Laura L. Smith, Stacey R. Gundry, Jessica E. McIntire, Junko Shimazu, Jessica R. Bass, Ethan A. Talbot, Leonela Amoasii, Nathaniel E. Goldman, Jocelyn Laporte, Alan H. Beggs
Review
Biochemistry & Molecular Biology
Karim Hnia, Tim Clausen, Christel Moog-Lutz
TRENDS IN MOLECULAR MEDICINE
(2019)