Article
Biology
Jan Eckhardt, Alexis Ruiz, Stephane Koenig, Maud Frieden, Herve Meier, Alexander Schmidt, Susan Treves, Francesco Zorzato
Summary: Skeletal muscles are responsible for movement and metabolic regulation. Congenital myopathies, caused by mutations in genes such as RYR1, lead to weak muscles. This study found that RYR1 mutations decrease RyR1 protein content and alter the expression of proteins involved in calcium signaling, metabolism, and ER protein quality control. It also identified potential targets for treating RyR1-related congenital myopathies.
Article
Clinical Neurology
Anna Sarkozy, Mario Sa, Deborah Ridout, Miguel Angel Fernandez-Garcia, Maria Grazia Distefano, Marion Main, Jennie Sheehan, Adnan Y. Manzur, Pinki Munot, Stephanie Robb, Elizabeth Wraige, Rosaline Quinlivan, Mariacristina Scoto, Giovanni Baranello, Vasantha Gowda, Rachael Mein, Rahul Phadke, Heinz Jungbluth, Francesco Muntoni
Summary: This study provides long-term data on the natural history of RYR1-related myopathies, with a focus on dominant and recessive forms of the disease. The results suggest that recessive patients have more severe clinical presentations, respiratory outcomes, and feeding outcomes compared to dominant patients. However, the longitudinal analysis indicates a slower progression of motor and respiratory function in recessive patients.
Article
Pharmacology & Pharmacy
Isabelle Marty, Mathilde Beaufils, Julien Faure, John Rendu
Summary: Myopathies associated with RYR1 gene variations are genetic disorders with limited treatment options. The large size and wide distribution of variations along the sequence make it challenging to develop effective therapies. However, advancements in gene therapy and gene editing tools provide potential solutions at the mRNA and DNA levels. Promising results have been obtained in in vitro and in vivo studies, and inspiration can be drawn from other genetic diseases for the development of novel gene editing techniques.
CURRENT OPINION IN PHARMACOLOGY
(2023)
Article
Clinical Neurology
Xingzhi Chang, Risheng Wei, Cuijie Wei, Jieyu Liu, Lun Qin, Hui Yan, Yinan Ma, Zhaoxia Wang, Hui Xiong
Summary: The correlation between phenotype and genotype in RYR1-related myopathy is complex, and is influenced by inheritance mode, variation type, and variant location. This study found that dominant and recessive variants impact different sensitive domains of RyR1 through different pathways.
FRONTIERS IN NEUROLOGY
(2022)
Article
Clinical Neurology
Eleonora Mauri, Daniela Piga, Alessandra Govoni, Roberta Brusa, Serena Pagliarani, Michela Ripolone, Robertino Dilena, Claudia Cinnante, Monica Sciacco, Denise Cassandrini, Vincenzo Nigro, Nereo Bresolin, Stefania Corti, Giacomo P. Comi, Francesca Magri
Summary: RYR1-RCM is the most common subgroup among congenital myopathies, presenting with high clinical heterogeneity. Early comprehensive characterization and genetic analysis are crucial for diagnosis and prompt medical management.
FRONTIERS IN NEUROLOGY
(2021)
Review
Pharmacology & Pharmacy
Mathilde Beaufils, Lauriane Travard, John Rendu, Isabelle Marty
Summary: RyR1-related myopathies are genetic neuromuscular diseases caused by mutations in the RYR1 gene, with no current treatment options. However, with the increasing number of preclinical assessments and clinical trials, there is hope for future therapeutic perspectives.
CURRENT PHARMACEUTICAL DESIGN
(2022)
Article
Physiology
Alexander Sonne, Anna Katarina Antonovic, Elise Melhedegaard, Fariha Akter, Jesper L. Andersen, Heinz Jungbluth, Nanna Witting, John Vissing, Edmar Zanoteli, Arianna Fornili, Julien Ochala
Summary: This study aimed to investigate whether mutations in the RYR1 gene, which is related to muscle disorders, affect the regulation of myosin. The results showed that these mutations may have negative consequences on the structure and function of myosin, contributing to the phenotype of congenital myopathy.
Article
Medicine, General & Internal
Luuk R. van den Bersselaar, Nick Kruijt, Gert-Jan Scheffer, Lucas van Eijk, Ignacio Malagon, Stan Buckens, Jose A. E. Custers, Leonie Helder, Anna Greco, Leo A. B. Joosten, Baziel G. M. van Engelen, Nens van Alfen, Sheila Riazi, Susan Treves, Heinz Jungbluth, Marc M. J. Snoeck, Nicol C. Voermans
Summary: This study aims to investigate the comprehensive neuromuscular and multisystem features of RYR1-related MH and ERM, establishing a well-characterized baseline cohort for future research. The study includes questionnaire surveys, clinical observations, imaging, and immunological studies.
Article
Clinical Neurology
Osorio Lopes Abath Neto, Livija Medne, Sandra Donkervoort, Maria Elena Rodriguez-Garcia, Veronique Bolduc, Ying Hu, Eleonora Guadagnin, A. Reghan Foley, John F. Brandsema, Allan M. Glanzman, Gihan Tennekoon, Mariarita Santi, Justin H. Berger, Lynn A. Megeney, Hirofumi Komaki, Michio Inoue, Francisco Javier Cotrina-Vinagre, Aurelio Hernandez-Lain, Elena Martin-Hernandez, Linford Williams, Sabine Borell, David Schorling, Kimberly Lin, Konstantinos Kolokotronis, Uta Lichter-Konecki, Janbernd Kirschner, Ichizo Nishino, Brenda Banwell, Francisco Martinez-Azorin, Patrick G. Burgon, Carsten G. Bonnemann
Summary: This study identified seven individuals from six families with biallelic variants in the MLIP gene, shedding light on the genetic landscape of rhabdomyolysis. The findings solidify MLIP's role in maintaining normal and diseased skeletal muscle homeostasis.
Article
Pharmacology & Pharmacy
Chris Lindsay, Maria Musgaard, Angela J. Russell, Rebecca Sitsapesan
Summary: This study found that all the statins examined could activate RyR1, and cerivastatin was the most potent in activating RyR1, supporting the hypothesis that RyR1 activation is implicated in statin-induced myopathy. Several statin analogues were identified that retained HMG-CoA reductase inhibition but lacked the ability to modulate RyR1.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Genetics & Heredity
Qingxian Deng, Zhongying Ding, Qinqin Fu, Meifang Lin
Summary: This case report identifies a congenital myopathy caused by a complex heterozygous mutation in the RYR1 gene and analyzes the pathogenicity of the mutation. The study retrospectively analyzed the clinical manifestations, laboratory examinations, imaging findings, muscle pathology, and gene test results of the patient, and discovered a new compound heterozygous variation in the RYR1 gene that expands the RYR1 gene spectrum.
Article
Neurosciences
Valerie Biancalana, John Rendu, Annabelle Chaussenot, Helen Mecili, Eric Bieth, Melanie Fradin, Sandra Mercier, Maud Michaud, Marie-Christine Nougues, Laurent Pasquier, Sabrina Sacconi, Norma B. Romero, Pascale Marcorelles, Francois Jerome Authier, Antoinette Gelot Bernabe, Emmanuelle Uro-Coste, Claude Cances, Bertrand Isidor, Armelle Magot, Marie-Christine Minot-Myhie, Yann Pereon, Julie Perrier-Boeswillwald, Gilles Bretaudeau, Nicolas Dondaine, Alison Bouzenard, Megane Pizzimenti, Bruno Eymard, Ana Ferreiro, Jocelyn Laporte, Julien Faure, Johann Bohm
Summary: The recurrent RYR1 mutation previously classified as VUS was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, providing evidence of its pathogenicity. This mutation causes an atypical congenital myopathy with slowly improving motor function over the first decades of life, indicating a potential for directing molecular diagnosis for patients with similar clinical presentation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Neurosciences
Fang-Yuan Qian, Yu-Dong Guo, Juan Zu, Jin-Hua Zhang, Yi-Ming Zheng, Idriss Ali Abdoulaye, Zhao-Hui Pan, Chun-Ming Xie, Han-Chao Gao, Zhi-Jun Zhang
Summary: A novel recessive mutation in the DNAJB6 gene was identified in a Chinese family with late onset distal myofibrillar myopathy, resulting in decreased mRNA and protein levels of DNAJB6a and age-dependent toxic effects on skeletal muscle. The mutant DNAJB6a also showed a dose-dependent anti-aggregation effect on polyglutamine-containing proteins in vitro, shedding light on the pathogenic role of DNAJB6a insufficiency in myofibrillar myopathies.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yukari Endo, Linda Groom, Sabrina M. Wang, Emanuela Pannia, Nigel W. Griffiths, Jenica L. M. Van Gennip, Brian Ciruna, Jocelyn Laporte, Robert T. Dirksen, James J. Dowling
Summary: CACNA1S-related myopathy is a congenital muscle disease with no effective therapies available. The lack of suitable animal models has hindered its study. Researchers have successfully generated zebrafish models that mimic key aspects of the severe and mild forms of the disease, providing a basis for future mechanistic studies and therapy development.
HUMAN MOLECULAR GENETICS
(2023)
Article
Clinical Neurology
Shahar Shelly, Niaz Talha, Naveen L. Pereira, Andrew G. Engel, Jonathan N. Johnson, Duygu Selcen
Summary: Patients with desmin-related myopathy may present with both neurologic and cardiac symptoms, usually starting in the third decade of life. Heart transplantation can be tolerated with improved cardiac function and quality of life.