Article
Biochemistry & Molecular Biology
Patrizia Spadafora, Antonio Qualtieri, Francesca Cavalcanti, Gemma Di Palma, Olivier Gallo, Selene De Benedittis, Annamaria Cerantonio, Luigi Citrigno
Summary: This study reports a new missense variant in the DYSF gene associated with LGMDR2/2B, identified through NGS technology. The variant was found in homozygosity in two sisters of the proband, indicating its probable pathological role in the onset of the disease. The study highlights the potential of NGS as a powerful tool for identifying LGMD subtypes and emphasizes the importance of collecting and sharing genetic data for further genetic-molecular research and personalized medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alan Rawls, Bridget K. Diviak, Cameron I. Smith, Grant W. Severson, Sofia A. Acosta, Jeanne Wilson-Rawls
Summary: Muscular dystrophies are genetic muscle-wasting disorders characterized by chronic inflammation and fibrotic scarring in muscle tissue. Duchenne muscular dystrophy, the most common form, is typically treated with anti-inflammatory glucocorticoids; however, their long-term use is limited by adverse side effects. Developing new pharmacotherapeutic approaches to reduce muscle damage and promote repair is crucial.
Article
Cell Biology
Brian J. Paleo, Kevin E. McElhanon, Hannah R. Bulgart, Kassidy K. Banford, Eric X. Beck, Kristina M. Sattler, Briana N. Goines, Shelby L. Ratcliff, Kelly E. Crowe, Noah Weisleder
Summary: TRIM72/MG53-mediated membrane repair can partially compensate for sarcolemmal fragility in DMD and the loss of membrane repair leads to increased pathology.
Article
Medicine, Research & Experimental
Sandra Donkervoort, Niklas Krause, Mykola Dergai, Pomi Yun, Judith Koliwer, Svetlana Gorokhova, Janelle Geist Hauserman, Beryl B. Cummings, Ying Hu, Rosemarie Smith, Prech Uapinyoying, Vijay S. Ganesh, Partha S. Ghosh, Kristin G. Monaghan, Seby L. Edassery, Pia E. Ferle, Sarah Silverstein, Katherine R. Chao, Molly Snyder, Sara Ellingwood, Diana Bharucha-Goebel, Susan T. Iannaccone, Matteo Dal Peraro, A. Reghan Foley, Jeffrey N. Savas, Veronique Bolduc, Dirk Fasshauer, Carsten G. Bonnemann, Michael Schwake
Summary: This study identifies BET1 as a novel gene associated with severe congenital muscular dystrophy (CMD) and epilepsy, revealing its role in protein transport and interaction with other partners. The variant p.(Ile51Ser) is found to affect BET1 protein binding and interaction with proteins like ERGIC-53. The findings support the emerging role of ER/Golgi SNAREs in CMD and shed light on potential mechanisms underlying these diseases.
EMBO MOLECULAR MEDICINE
(2021)
Article
Genetics & Heredity
Feng Zhu, Fengxiao Zhang, Lizhi Hu, Haowen Liu, Yahua Li
Summary: This study reported two siblings in a family with different NMDs, identifying a novel mutation in the Dysferlin gene through WES, and discovering a deep intronic mutation through integrated RNA-seq and WGS. The results highlight the importance of using RNA-seq and WGS together for the diagnosis of hereditary NMDs.
FRONTIERS IN GENETICS
(2021)
Article
Medicine, Research & Experimental
Alexis R. Demonbreun, Elena Bogdanovic, Lauren A. Vaught, Nina L. Reiser, Katherine S. Fallon, Ashlee M. Long, Claire C. Oosterbaan, Michele Hadhazy, Patrick G. T. Page, Prem Raj B. Joseph, Gabrielle Cowen, Alexander M. Telenson, Ammaarah Khatri, Katherine R. Sadleir, Robert Vassar, Elizabeth M. McNally
Summary: Annexin A6 plays a crucial role in membrane repair and can promote repair in multiple cell types. Recombinant annexin A6 may have potential in treating chronic disorders.
Article
Biochemistry & Molecular Biology
Zsuzsanna Szucs, Eva Pinti, Iren Haltrich, Orsolya Palne Szen, Tibor Nagy, Endre Barta, Gabor Mehes, Laszlo Bidiga, Olga Torok, Aniko Ujfalusi, Katalin Koczok, Istvan Balogh
Summary: Duchenne muscular dystrophy (DMD) is the most common inherited muscle dystrophy, typically affecting males. This study presents an ultra-rare manifestation of DMD in a female patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Geriatrics & Gerontology
Francesca M. Alves, Kai Kysenius, Marissa K. Caldow, Justin P. Hardee, Jin D. Chung, Jennifer Trieu, Dominic J. Hare, Peter J. Crouch, Scott Ayton, Ashley Bush, Gordon S. Lynch, Rene Koopman
Summary: Muscle tissues from dystrophic mice showed increased iron levels and dysregulated iron-related proteins associated with the pathology. Muscle iron levels were manipulated by iron chelation and iron-enriched feed, with chelation reducing fibrosis and reactive oxygen species but suppressing certain proteins, while iron supplementation increased specific proteins without altering other aspects of pathology.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Cell Biology
Yu Zhang, Christopher Zeuthen, Carol Zhu, Fang Wu, Allison T. Mezzell, Thomas J. Whitlow, Hyojung J. Choo, Katherine E. Vest
Summary: Oculopharyngeal muscular dystrophy (OPMD) is a late-onset dominant disease primarily affecting craniofacial muscles with no current pharmacologic treatments available. Using a mouse model, this study discovered pathology in pharyngeal muscles and satellite cells, suggesting aberrant gain of PABPN1 function contributes to the craniofacial pathology in OPMD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Qian Ban, Peng Yang, Shih-Jie Chou, Li Qiao, Haidong Xia, Jingjing Xue, Fang Wang, Xiaobin Xu, Na Sun, Ryan Y. Zhang, Ceng Zhang, Athena Lee, Wenfei Liu, Ting-Yi Lin, Yu-Ling Ko, Petar Antovski, Xinyue Zhang, Shih-Hwa Chiou, Chin-Fa Lee, Wenqiao Hui, Dahai Liu, Steven J. Jonas, Paul S. Weiss, Hsian-Rong Tseng
Summary: CRISPR/Cas9 technology offers a versatile solution for treating genetic diseases through efficient and precise gene editing. A nonviral delivery strategy involving encapsulating Cas9·sgRNA ribonucleoprotein complexes into supramolecular nanoparticles has shown promise in targeted cell delivery, demonstrating efficient gene disruption in various cell types.
Article
Clinical Neurology
Ursula Moore, Roberto Fernandez-Torron, Marni Jacobs, Heather Gordish-Dressman, Jordi Diaz-Manera, Meredith K. James, Anna G. Mayhew, Elizabeth Harris, Michela Guglieri, Laura E. Rufibach, Jia Feng, Andrew M. Blamire, Pierre G. Carlier, Simone Spuler, John W. Day, Kristi J. Jones, Diana X. Bharucha-Goebel, Emmanuelle Salort-Campana, Alan Pestronk, Maggie C. Walter, Carmen Paradas, Tanya Stojkovic, Madoka Mori-Yoshimura, Elena Bravver, Elena Pegoraro, Linda Pax Lowes, Jerry R. Mendell, Kate Bushby, John Bourke, Volker Straub
Summary: This study aimed to determine whether respiratory or cardiac dysfunction is part of the dysferlinopathy phenotype. Objective measures of respiratory and cardiac function were collected in 188 genetically confirmed patients. The results showed clinically significant respiratory impairment and abnormal atrial conduction in some patients. Therefore, regular assessment of respiratory and cardiac function is recommended for these patients.
Article
Biochemistry & Molecular Biology
Pierre Meyer, Cecile Notarnicola, Albano C. Meli, Stefan Matecki, Gerald Hugon, Jeremy Salvador, Mirna Khalil, Leonard Feasson, Claude Cances, Jerome Cottalorda, Isabelle Desguerre, Jean-Marie Cuisset, Pascal Sabouraud, Alain Lacampagne, Hugues Chevassus, Francois Rivier, Gilles Carnac
Summary: The study highlights the role of RYR1-mediated Ca2+ leakage in human DMD myotubes and suggests that RYR1 stabilization may be a promising therapeutic strategy for DMD. The findings indicate that impaired myogenic differentiation in DMD is associated with altered RYR1-mediated Ca2+ release and suggests a potential relationship between RYR1 dysfunction and motor impairment in patients with DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Ainoa Tejedera-Villafranca, Marisol Montolio, Javier Ramon-Azcon, Juan M. Fernandez-Costa
Summary: This study developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality and mirror the pathological myotube breakdown in DMD. The study also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues. The findings highlight the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies.
Article
Medicine, Research & Experimental
Andres Ramirez-Martinez, Yichi Zhang, Marie-Jose Van den Boogaard, John R. McAnally, Cristina Rodriguez-Caycedo, Andreas C. Chai, Francesco Chemello, Maarten P. G. Massink, Inge Cuppen, Martin G. Elferink, Robert J. J. van Es, Nard G. Janssen, Linda P. A. M. Walraven-van Oijen, Ning Liu, Rhonda Bassel-Duby, Richard H. van Jaarsveld, Eric N. Olson
Summary: The study identifies a variant of the MYMX gene that is associated with CFZS-like abnormalities, leading to impaired fusion activity. Patient-derived cells and mouse models confirm the pathogenic role of this variant and CRISPR/Cas9 gene editing shows potential for therapeutic intervention.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Genetics & Heredity
Hamidreza Mianesaz, Safoura Ghalamkari, Mansoor Salehi, Mahdiyeh Behnam, Majid Hosseinzadeh, Keivan Basiri, Majid Ghasemi, Maryam Sedghi, Behnaz Ansari
Summary: In this study, next-generation sequencing was used to diagnose limb-girdle muscular dystrophy in 26 Iranian patients. Six novel disease-causing variants were identified, some of which affected highly conserved regions of amino acid sequence.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Elizabeth McNally
Article
Cardiac & Cardiovascular Systems
Anthony M. Gacita, Dominic E. Fullenkamp, Joyce Ohiri, Tess Pottinger, Megan J. Puckelwartz, Marcelo A. Nobrega, Elizabeth M. McNally
Summary: This study identified enhancers that regulate cardiomyopathy gene expression by integrating epigenomic profiling from hearts and cardiomyocytes. Genomic variation within these enhancer regions is associated with cardiomyopathy progression over time, highlighting the importance of noncoding modifiers in cardiac diseases.
Editorial Material
Medicine, Research & Experimental
Jamie R. Johnston, Daniel F. Selgrade, Elizabeth M. McNally
Summary: Mutations in the LMNA gene are a common cause of adult-onset cardiomyopathy and heart failure, with a prenatal feature of impaired cardiomyocyte development and maturation identified in a Laminopathy model. Treatment of the LMNA H222P mouse model improved congenital cardiomyopathy and increased survival in utero, presenting a unique therapeutic strategy for cardiomyopathy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Cardiac & Cardiovascular Systems
Arjun Sinha, Deepak K. Gupta, Clyde W. Yancy, Sanjiv J. Shah, Laura J. Rasmussen-Torvik, Elizabeth M. McNally, Philip Greenland, Donald M. Lloyd-Jones, Sadiya S. Khan
Summary: The article highlights the need for targeted prevention of heart failure, emphasizing the importance of quantifying individual patient risks in devising optimal prevention strategies. It discusses the development of HF risk prediction tools and the role of biomarkers in personalized risk estimation, as well as explores the application of genomics-enhanced approaches for HF prevention.
CIRCULATION-HEART FAILURE
(2021)
Editorial Material
Cardiac & Cardiovascular Systems
Dominic E. Fullenkamp, Megan J. Puckelwartz, Elizabeth M. McNally
EUROPEAN HEART JOURNAL
(2021)
Article
Clinical Neurology
Alexis R. Demonbreun, Matthew P. Velez, Rana Saber, Daniel T. Ryan, Amelia Sancilio, Thomas W. McDade, Elizabeth M. McNally
Summary: Non-ambulatory neuromuscular disease patients show a strong immune response to two doses of mRNA COVID-19 vaccine, as indicated by elevated antibody levels similar to healthy vaccinated controls.
NEUROMUSCULAR DISORDERS
(2022)
Article
Cardiac & Cardiovascular Systems
Rabia S. Khan, Elfriede Pahl, Lisa Dellefave-Castillo, Karen Rychlik, Alexander Ing, Kai Lee Yap, Casey Brew, Jamie R. Johnston, Elizabeth M. McNally, Gregory Webster
Summary: Pediatric dilated cardiomyopathy (DCM) is a common cardiac disease, but the correlation between its phenotype and genotype is poorly understood. This study reviewed a large number of pediatric DCM cases and found that variations in sarcomeric genes are associated with age of diagnosis and cardiac outcomes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Immunology
Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Manoj Panta, Ashok D. Prabakaran, Grant D. Barish, Navdeep S. Chandel, Elizabeth M. McNally
Summary: This study found that intermittent use of glucocorticoids can improve metabolic status, exercise tolerance, and energy expenditure in mice with diet-induced obesity. These effects are associated with the regulation of adiponectin, and are achieved through the modulation of glucocorticoid receptor and the CAMKK2-AMPK cascade in muscle metabolism.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Alexis R. Demonbreun, Elena Bogdanovic, Lauren A. Vaught, Nina L. Reiser, Katherine S. Fallon, Ashlee M. Long, Claire C. Oosterbaan, Michele Hadhazy, Patrick G. T. Page, Prem Raj B. Joseph, Gabrielle Cowen, Alexander M. Telenson, Ammaarah Khatri, Katherine R. Sadleir, Robert Vassar, Elizabeth M. McNally
Summary: Annexin A6 plays a crucial role in membrane repair and can promote repair in multiple cell types. Recombinant annexin A6 may have potential in treating chronic disorders.
Editorial Material
Cardiac & Cardiovascular Systems
Elizabeth M. McNally, Karisma R. Chhabria, Dominic E. Fullenkamp
CIRCULATION-HEART FAILURE
(2023)
Editorial Material
Physiology
David Y. Barefield
Summary: Reduced expression of MYBPC3 leads to early dysfunction in human cell culture models, even before reduced levels of cMyBP-C.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
David Y. Y. Barefield, Alejandro Alvarez-Arce, Kelly N. N. Araujo
Summary: The pace of identifying cardiomyopathy-associated mutations and advances in our understanding of sarcomere function that underlies many cardiomyopathies has led to promising new treatments being developed. Recent findings include the identification of new genes linked to cardiomyopathy and advancements in our understanding of sarcomere function.
CURRENT CARDIOLOGY REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Lisa M. Wren, Jean-Marc Dekeyser, David Y. Barefield, Nicole A. Hawkins, Elizabeth M. Mcnally, Jennifer A. Kearney, J. Andrew Wasserstrom, Alfred L. George Jr
Summary: This study investigates the effects of different factors on the phenotype of calmodulinopathy and reveals the heterogeneity in arrhythmia susceptibility and cardiomyocyte Ca2+ dynamics among male and female mice with a recurrent pathogenic variant in Calm1 or Calm2.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Isabella M. Salamone, Mattia Quattrocelli, David Y. Barefield, Patrick G. Page, Ibrahim Tahtah, Michele Hadhazy, Garima Tomar, Elizabeth M. McNally
Summary: Weekly glucocorticoid exposure produces different effects on skeletal muscle performance in male and female mice. Male muscles show enhanced response to weekly glucocorticoids, while female muscles exhibit significant upregulation of lipid metabolism genes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)