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)
Review
Genetics & Heredity
Laura Morant, Maria-Luise Erfurth, Albena Jordanova
Summary: CMT is a common neuromuscular disorder, with aaRS mutations causing different subtypes and similar clinical manifestations. Drosophila models are valuable for studying the molecular pathways of CMT and testing candidate drugs.
Article
Clinical Neurology
Jin He, Xiao-Xuan Liu, Ming-Ming Ma, Jing-Jing Lin, Jun Fu, Yi-Kun Chen, Guo-Rong Xu, Liu-Qing Xu, Zhi-Fei Fu, Dan Xu, Wen-Feng Chen, Chun-Yan Cao, Yan Shi, Yi-Heng Zeng, Jing Zhang, Xiao-Chun Chen, Ru-Xu Zhang, Ning Wang, Marina Kennerson, Dong-Sheng Fan, Wan-Jin Chen
Summary: This study identified causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) that were associated with Charcot-Marie-Tooth (CMT) disease. Whole-exome sequencing and linkage analysis revealed the correlation between these mutations and the clinical phenotype in affected families. Experimental evidence demonstrated that the mutant SerRS proteins had reduced aminoacylation activity and abnormal dimerization, leading to impaired protein synthesis and induction of eIF2 alpha phosphorylation.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Yanyu Lu, Haiying Xing, Chang Liu, Diandian Huang, Chengyue Sun, Meng Yu, Lingchao Meng, He Lv, Wei Zhang, Zhaoxia Wang, Yun Yuan, Zhiying Xie
Summary: This study reports two patients with pathogenic PSAT1 variants presenting only as polyneuropathy and ichthyosis. Whole exome sequencing identified homozygous and compound heterozygous variants in the PSAT1 gene in the two patients. Nerve conduction studies revealed severe motor neuropathy with mitochondrial abnormalities. Both pathogenic PSAT1 variants were classified as likely pathogenic or pathogenic according to standard guidelines. This study confirms that pathogenic PSAT1 variants can cause a mild phenotype of axonal Charcot-Marie-Tooth disease.
PEDIATRIC NEUROLOGY
(2023)
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
Biochemistry & Molecular Biology
Laura Morant, Maria-Luise Petrovic-Erfurth, Albena Jordanova
Summary: By utilizing the improved GeneSwitch(TM) technology, we were able to regulate transgene expression in mammalian cells and fruit fly models, leading to the generation of phenotypes resembling YARS1-induced Charco-Marie-Tooth neuropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
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.
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
Han Zhang, Zhong-Wei Zhou, Litao Sun
Summary: Charcot-Marie-Tooth disease (CMT) is a common inherited neurodegenerative disorder with an increasing number of identified CMT-associated variants as causative factors. Recent studies have shown that in CMT, variants of Aminoacyl-tRNA synthetases (aaRS) can lead to toxic gain-of-function, and not all variants are due to the loss of aminoacylation activity. Researching the functions of these CMT-related AaRS variants is crucial for understanding the pathogenesis of CMT.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Anatomy & Morphology
Timothy J. Hines, Abigail L. D. Tadenev, Museer A. Lone, Courtney L. Hatton, Inseyah Bagasrawala, Morgane G. Stum, Kathy E. Miers, Thorsten Hornemann, Robert W. Burgess
Summary: Animal models of inherited peripheral neuropathies can accurately recreate the pathophysiology or genetic perturbations found in patients, but not always both simultaneously. The described Yars(E196K) and Sptlc1(C133W) mouse models each exhibit certain disease-relevant phenotypes, but show differences in reproducing human genetics and disease phenotypes. Despite these limitations, both models offer valuable insights for future research.
JOURNAL OF ANATOMY
(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
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.
