Article
Clinical Neurology
Andrea Cortese, Riccardo Curro, Riccardo Ronco, Julian Blake, Alex M. Rossor, Enrico Bugiardini, Matilde Laura, Tom Warner, Tarek Yousry, Roy Poh, James Polke, Adriana Rebelo, Maike F. Dohrn, Mario Saporta, Henry Houlden, Stephan Zuchner, Mary M. Reilly
Summary: Mutations in the CRYAB gene have been associated with myofibrillar myopathy, dilated cardiomyopathy, and cataracts. This study reports peripheral neuropathy as a novel phenotype associated with CRYAB, particularly in cases with late onset CMT2 and congenital cataracts.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Neurosciences
Tara C. Tassin, Barbara Barylko, Per Niklas Hedde, Yan Chen, Derk D. Binns, Nicholas G. James, Joachim D. Mueller, David M. Jameson, Ronald Taussig, Joseph P. Albanesi
Summary: Mutations in the DNM2 gene are associated with motor disorders affecting nerve and muscle, such as CMT and CNM; CMT and CNM mutations have distinct effects on DNM2 function, suggesting different pathogenic mechanisms and genetic overlap should be re-examined.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Marina Stavrou, Irene Sargiannidou, Elena Georgiou, Alexia Kagiava, Kleopas A. Kleopa
Summary: CMT disease is a genetically heterogeneous disorder affecting the peripheral nerves, with diverse molecular genetic mechanisms discovered over the past three decades. There are currently various treatment approaches in preclinical testing and clinical trials, including disease-specific targeted therapies and treatments targeting common pathways shared by different CMT types. As promising treatments advance to clinical translation, optimizing outcome measures, novel biomarkers, and appropriate trial designs are crucial to facilitate successful testing and validation of novel treatments for CMT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Cara R. Schiavon, Gerald S. Shadel, Uri Manor
Summary: CMT disease is a progressive, inherited neurological disorder associated with mutations in at least 80 different genes. Clinical manifestations typically involve peripheral neurons, with some mutations potentially leading to mitochondrial mobility defects, suggesting a common underlying disease mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Clinical Neurology
Brett A. McCray, Steven S. Scherer
Summary: Inherited peripheral neuropathies are a group of genetically and phenotypically diverse disorders that result in degeneration of peripheral neurons, leading to sensory and motor dysfunction. Recent research has identified common pathological mechanisms among these diseases, including defects in axonal transport, mitochondrial dynamics, organelle-organelle contacts, and local axonal protein translation. These insights have informed emerging treatment strategies for inherited neuropathies, offering promising therapeutic opportunities.
Article
Clinical Neurology
Alessandro Bertini, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Matteo Tagliapietra, Marina Grandis, Stefano Carlo Previtali, Yuri Matteo Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Irene Tramacere, Eleonora Cavalca, Paola Saveri, Andrea Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Valeria Prada, Riccardo Zuccarino, Francesco Ferraro, Chiara Pisciotta, Davide Pareyson, Italian CMT Network
Summary: This study investigated the use, benefits, and tolerance of shoe inserts, orthopaedic shoes, and ankle-foot orthoses (AFOs) in Charcot-Marie-Tooth disease (CMT) patients. The results showed that although most patients were prescribed these devices, there was a low usage rate and high rates of complications and emotional distress, leading to reduced use of AFOs. Thus, a patient-oriented and multidisciplinary approach to orthoses prescription should be encouraged.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Clinical Neurology
Silvia Cipriani, Marta Guerrero-Valero, Stefano Tozza, Edward Zhao, Veith Vollmer, Danique Beijer, Matt Danzi, Cristina Rivellini, Dejan Lazarevic, Giovanni Battista Pipitone, Bianca Rose Grosz, Costanza Lamperti, Stefania Bianchi Marzoli, Paola Carrera, Marcella Devoto, Chiara Pisciotta, Davide Pareyson, Marina Kennerson, Stefano C. Previtali, Stephan Zuchner, Steven S. Scherer, Fiore Manganelli, Martin Bahler, Alessandra Bolino
Summary: The study identified that novel or very rare variants in the MYO9B gene are associated with CMT2 and isolated OA. Functional studies showed that variants in MYO9B impair protein expression level and motor activity, indicating its essential role in peripheral and central nervous system axons.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Christopher P. Ptak, Tabitha A. Peterson, Jesse B. Hopkins, Christopher A. Ahern, Michael E. Shy, Robert C. Piper
Summary: Mutations in MPZ can cause various neurological disorders, and the study focuses on understanding how MPZ functions and forms oligomeric assemblies.
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
Health Care Sciences & Services
Jihyun Park, So Young Joo, Byung-Ok Choi, Dae-Hyun Kim, Jong Bum Park, Jong Weon Lee, Deog Young Kim
Summary: This study evaluated the characteristics of gait patterns in CMT1A patients and classified them according to disease severity. The results showed significant differences in gait parameters between CMT1A patients and healthy controls, as well as variations in gait patterns within different severity groups.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
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
Clinical Neurology
Luce Barbat du Closel, Nathalie Bonello-Palot, Yann Pereon, Andoni Echaniz-Laguna, Jean Philippe Camdessanche, Aleksandra Nadaj-Pakleza, Jean-Baptiste Chanson, Simon Frachet, Laurent Magy, Julien Cassereau, Pascal Cintas, Ariane Choumert, Perrine Devic, Sarah Leonard Louis, Robinson Gravier Dumonceau, Emilien Delmont, Emmanuelle Salort-Campana, Francoise Bouhour, Philippe Latour, Tanya Stojkovic, Shahram Attarian
Summary: This study investigated the clinical presentation of patients with CMTX1 and found that women usually have milder clinical symptoms compared to men. The study also identified two subgroups of women over the age of 48, with one group showing similar disease progression to men.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Lucas Bayones, Maria Jose Guerra-Fernandez, Fernando Hinostroza, Ximena Baez-Matus, Jacqueline Vasquez-Navarrete, Luciana Gallo, Sergio Parra, Agustin D. Martinez, Arlek Gonzalez-Jamett, Fernando D. Marengo, Ana M. Cardenas
Summary: Gain-of-function mutations of dynamin-2 result in centronuclear myopathy by impairing exocytosis, disrupting actin filament formation and impacting the plasmalemma expression of functional proteins in skeletal muscle cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Hye Mi Kwon, Hyun Su Kim, Sang Beom Kim, Jae Hong Park, Da Eun Nam, Ah Jin Lee, Soo Hyun Nam, Soohyun Hwang, Ki Wha Chung, Byung-Ok Choi
Summary: Through studying Korean CMT families, it was found that mutations in the GNB4 gene can cause not only intermediate type CMT, but also demyelinating-type neuropathy. Patients with the p.Lys89Glu mutation exhibited distinct demyelinating pathologic features and abnormalities in muscle MRI. Therefore, these findings are helpful for the differential diagnosis of CMT patients with unknown GNB4 variants.
Article
Clinical Neurology
Lara El-Bazzal, Adeline Ghata, Clothilde Esteve, Jihane Gadacha, Patrice Quintana, Christel Castro, Nathalie Roeckel-Trevisiol, Frederique Lembo, Nicolas Lenfant, Andre Megarbane, Jean-Paul Borg, Nicolas Levy, Marc Bartoli, Yannick Poitelon, Pierre L. Roubertoux, Valerie Delague, Nathalie Bernard-Marissal
Summary: Charcot-Marie-Tooth (CMT) disease is a common inherited neurological disorder caused by mutations in over 100 genes. A study found that mutations in the FGD4 gene, which encodes FRABIN, can lead to aberrant myelination in the peripheral nervous system. The loss of FRABIN affects the NRG1/ERBB2/3 signaling pathway and impairs endocytic trafficking, contributing to myelination defects.
Article
Clinical Neurology
Bernardita Suarez, Javiera Jofre, Andres Lozano-Arango, Ximena Ortega, Jorge Diaz, Giancarlo Calcagno, Jorge A. Bevilacqua, Claudia Castiglioni
NEUROMUSCULAR DISORDERS
(2020)
Review
Clinical Neurology
Jorge Arriagada-Diaz, Lorena Prado-Vega, Ana M. Cardenas Diaz, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: Dynamin superfamily proteins play important roles in synaptic transmission and plasticity by regulating synaptic vesicle recycling and neurotransmitter release. Mutations and dysfunction of these proteins are associated with various neurological disorders.
Letter
Clinical Neurology
Jorge A. Bevilacqua, Edoardo Malfatti, Emence Labasse, Guy Brochier, Angeline Madelaine, Emmanuelle Lacene, Berenice Doray, Pascal Laforet, Bruno Eymard, John Rendu, Norma B. Romero
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Jorge A. Bevilacqua, Liz M. Rujano, Alejandra Trangulao, Jorge A. Munoz, Lorena Acevedo
NEUROMUSCULAR DISORDERS
(2021)
Article
Biochemistry & Molecular Biology
Arlek Gonzalez-Jamett, Walter Vasquez, Gabriela Cifuentes-Riveros, Rafaela Martinez-Pando, Juan C. Saez, Ana M. Cardenas
Summary: Muscular dystrophies are a heterogeneous group of neuromuscular disorders characterized by muscle pain, weakness, and atrophy. These diseases are caused by gene mutations that affect the structure and function of skeletal muscles, leading to inflammation, oxidative stress, and muscle degeneration. Dysregulation of connexin hemichannels plays a crucial role in these processes.
Article
Clinical Neurology
Jorge A. Bevilacqua, Juan Pablo Contreras, Alejandra Trangulao, Ursula Hernandez, Guy Brochier, Jorge Diaz, Ricardo Hughes, Mario Campero, Norma B. Romero
Summary: This article reports a case of a 47-year-old male patient with polycythemia and restricted lung function, requiring ventilatory support. Physical examination revealed multiple muscle weakness and skeletal abnormalities, while whole-body MRI showed diffuse fatty replacement. Genetic sequencing identified a mutation in the TPM3 gene. Muscle biopsy revealed a novel histological pattern. These findings support the pathogenicity of the novel TPM3 variant.
NEUROMUSCULAR DISORDERS
(2022)
Article
Clinical Neurology
Marianela Schiava, Chiseko Ikenaga, Rocio Nur Villar-Quiles, Marta Caballero-Avila, Ana Topf, Ichizo Nishino, Virginia Kimonis, Bjarne Udd, Benedikt Schoser, Edmar Zanoteli, Paulo Victor Sgobbi Souza, Giorgio Tasca, Thomas Lloyd, Adolfo Lopez-de Munain, Carmen Paradas, Elena Pegoraro, Aleksandra Nadaj-Pakleza, Jan De Bleecker, Umesh Badrising, Alicia Alonso-Jimenez, Anna Kostera-Pruszczyk, Francesc Miralles, Jin-Hong Shin, Jorge Alfredo Bevilacqua, Montse Olive, Matthias Vorgerd, Rudi Kley, Stefen Brady, Timothy Williams, Cristina Dominguez-Gonzalez, George K. Papadimas, Jodi Warman, Kristl G. Claeys, Marianne de Visser, Nuria Muelas, Pascal LaForet, Edoardo Malfatti, Lindsay N. Alfano, Sruthi S. Nair, Georgios Manousakis, Hani A. Kushlaf, Matthew B. Harms, Christopher Nance, Alba Ramos-Fransi, Carmelo Rodolico, Channa Hewamadduma, Hakan Cetin, Jorge Garcia-Garcia, Endre Pal, Maria Elena Farrugia, Phillipa J. Lamont, Colin Quinn, Velina Nedkova-Hristova, Stojan Peric, Sushan Luo, Anders Oldfors, Kate Taylor, Stuart Ralston, Tanya Stojkovic, Conrad Weihl, Jordi Diaz-Manera
Summary: This study characterized patients with VCP gene mutations and investigated genotype-phenotype correlations, finding common symptoms and genetic variants. Specific genetic variants showed trends in affecting age of onset and severity. Additionally, the study provided valuable information on disease progression risk factors.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Article
Genetics & Heredity
Mathieu Cerino, Patricio Gonzalez-Hormazabal, Mario Abaji, Sebastien Courrier, Francesca Puppo, Yves Mathieu, Alejandra Trangulao, Nicholas Earle, Claudia Castiglioni, Jorge Diaz, Mario Campero, Ricardo Hughes, Carmen Vargas, Rocio Cortes, Karin Kleinsteuber, Ignacio Acosta, J. Andoni Urtizberea, Nicolas Levy, Marc Bartoli, Martin Krahn, Lilian Jara, Pablo Caviedes, Svetlana Gorokhova, Jorge A. Bevilacqua
Summary: This study reported the genetic findings of Chilean patients with limb-girdle muscle weakness. They identified definite genetic diagnoses in 59.8% of the patients and highly probable genetic diagnoses in 9.8% of the patients. The most frequent causative genes were DYSF and CAPN3. The relative frequency of different forms of myopathy in Chile is similar to that in other regions.
Article
Biochemistry & Molecular Biology
Lucas Bayones, Maria Jose Guerra-Fernandez, Fernando Hinostroza, Ximena Baez-Matus, Jacqueline Vasquez-Navarrete, Luciana Gallo, Sergio Parra, Agustin D. Martinez, Arlek Gonzalez-Jamett, Fernando D. Marengo, Ana M. Cardenas
Summary: Gain-of-function mutations of dynamin-2 result in centronuclear myopathy by impairing exocytosis, disrupting actin filament formation and impacting the plasmalemma expression of functional proteins in skeletal muscle cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Carolina Flores-Munoz, Francisca Garcia-Rojas, Miguel A. Perez, Odra Santander, Elena Mery, Stefany Ordenes, Javiera Illanes-Gonzalez, Daniela Lopez-Espindola, Arlek M. Gonzalez-Jamett, Marco Fuenzalida, Agustin D. Martinez, Alvaro O. Ardiles
Summary: Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies. The absence of Panx1 in the adult brain promotes structural and functional modifications in hippocampal synapses, preserving spontaneous activity. These modifications are related to actin-cytoskeleton dynamics and Rho GTPases.
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigates the effect of the dynamin-2 p.R465W mutation on CNS function and suggests that it disrupts synaptic and cognitive function. The mutation leads to changes in neuronal morphology and impaired excitatory synaptic transmission.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Claudia Garcia-Rodriguez, Paula Mujica, Javiera Illanes-Gonzalez, Araceli Lopez, Camilo Vargas, Juan C. Saez, Arlek Gonzalez-Jamett, Alvaro O. Ardiles
Summary: Probenecid, an old uricosuric agent, has been used to treat gout and reduce renal excretion of antibiotics. Recent studies have shown that Probenecid has the ability to interact with membrane proteins, indicating potential therapeutic applications in medicine. It has been found to have neuroprotective, antiepileptic, and anti-inflammatory properties, making it useful in the treatment of neurological and neurodegenerative diseases. Despite its declining clinical use, Probenecid shows promise in preclinical research as a strategy to enhance drug bioavailability in the central nervous system.
Article
Clinical Neurology
Jorge Arriagada-Diaz, Carolina Flores-Munoz, Barbara Gomez-Soto, Marjorie Labrana-Allende, Michelle Mattar-Araos, Lorena Prado-Vega, Fernando Hinostroza, Ivana Gajardo, Maria Jose Guerra-Fernandez, Jorge A. Bevilacqua, Ana M. Cardenas, Marc Bitoun, Alvaro O. Ardiles, Arlek M. Gonzalez-Jamett
Summary: This study investigated the effect of a mutation in the dynamin-2 gene on central nervous system function. The mutation was found to reduce dendritic arborisation and spine density, as well as impair excitatory synaptic transmission and recognition memory in a mouse model. These findings highlight the role of dynamin-2 in regulating neuronal morphology and synaptic transmission in the hippocampus.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2023)