Review
Biochemistry & Molecular Biology
Martijn van de Locht, Tamara C. Borsboom, Josine M. Winter, Coen A. C. Ottenheijm
Summary: Variants in skeletal troponin encoding genes can compromise sarcomere function, with potential therapeutic strategies including troponin activators and gene therapy. The pathophysiological effects of these variants are not fully understood, emphasizing the need for further research into treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Mariana I. Munoz-Garcia, Maria Paz Guerrero-Molina, Carlos Pablo de Fuenmayor-Fernandez de la Hoz, Laura Bermejo-Guerrero, Ana Arteche-Lopez, Aurelio Hernandez-Lain, Miguel A. Martin, Cristina Dominguez-Gonzalez
Summary: This study reported 3 cases of congenital myasthenic syndromes (CMS) initially misdiagnosed as primary mitochondrial myopathies (PMM). The patients presented with ptosis, external ophthalmoplegia, limb weakness, and fatigue. Early identification of CMS is crucial for effective medical treatment.
JOURNAL OF CLINICAL MEDICINE
(2023)
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
Clinical Neurology
Nika Maani, Sophie Karolczak, James J. Dowling
Summary: The field of genetic therapies is rapidly advancing, with the first gene-based treatments now in clinical practice. While there are currently no approved drug therapies for congenital myopathies, several candidate therapeutics, including gene replacement therapy and antisense oligonucleotide-based gene knockdown, are in development. Genetic therapies are bringing precision medicine to neurological diseases, with congenital myopathies being ideally suited for these approaches.
CURRENT OPINION IN NEUROLOGY
(2021)
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)
Article
Clinical Neurology
Qiang Gang, Conceicao Bettencourt, Stefen Brady, Janice L. Holton, Estelle G. Healy, John McConville, Patrick J. Morrison, Michela Ripolone, Raffaella Violano, Monica Sciacco, Maurizio Moggio, Marina Mora, Renato Mantegazza, Simona Zanotti, Zhaoxia Wang, Yun Yuan, Wei-wei Liu, David Beeson, Michael Hanna, Henry Houlden
Summary: This study identified genetic variants associated with myopathies with tubular aggregates (TAs) and demonstrated the potential role of ALG14 variants in TAs pathogenesis through cell experiments. The findings expand the phenotypic and genotypic spectrums of myopathies with TAs and support the hypothesis that genes related to calcium signaling pathway and N-linked glycosylation pathway are key genetic causes of TAs.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Clinical Neurology
Luke Perry, Georgia Stimpson, Leeha Singh, Jasper M. Morrow, Sachit Shah, Giovanni Baranello, Francesco Muntoni, Anna Sarkozy
Summary: The objective of this study was to evaluate the diagnostic and prognostic value of muscle MRI patterns as biomarkers in a genetically heterogeneous nemaline myopathy cohort. A total of 27 patients with MRI were included in the study, and distinct muscle involvement patterns were identified for NEB-NM, ACTA1-NM, and TPM3-NM genotypes. The findings suggest that these patterns may serve as diagnostic and prognostic biomarkers and aid in genetic variant interpretation.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
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
Maria Joao Pinto, Barbara Alves Passos, Ana Grangeia, Joana Guimaraes, Luis Braz
Summary: In this study, the majority of congenital myopathies (CM) patients were diagnosed in adulthood, despite having symptoms since childhood and a positive family history. The diagnostic delay may be attributed to mild symptoms, slow progression, atypical muscle histology, and lack of awareness about adult-onset CM. Larger studies are needed to further explore this topic.
ACTA NEUROLOGICA SCANDINAVICA
(2022)
Article
Neurosciences
Constantinos Papadopoulos, George K. Papadimas
Summary: Blepharoptosis can be classified into various types based on etiology, with primary myopathic diseases being a rare cause. This study reports four cases where blepharoptosis was the presenting symptom of different myopathic disorders. Patients with blepharoptosis and myopathy may face diagnostic errors and difficulties, but certain signs such as lack of symptom aggravation by fatigue and response to cholinesterase inhibitors treatment should prompt evaluation for an underlying myopathy.
Article
Oncology
Massimo Ganassi, Francesco Muntoni, Peter S. Zammit
Summary: This study explores the effects of pathogenic mutations on satellite cell function in muscle diseases. The findings suggest that these mutations can directly or indirectly affect satellite cell function, leading to muscle pathology. The study introduces a classification of satellite cell-opathies, which helps in diagnosis, prognosis, and treatment development.
EXPERIMENTAL CELL RESEARCH
(2022)
Article
Pediatrics
Yu Zhang, Hui Yan, Jieyu Liu, Huifang Yan, Yinan Ma, Cuijie Wei, Zhaoxia Wang, Hui Xiong, Xingzhi Chang
Summary: This study aimed to characterize congenital myopathies with infancy onset among patients registered at the institution. The results showed that the severity of congenital myopathies may vary among patients from different ethnic groups. The study also emphasized the importance of cardiac monitoring in patients with congenital myopathies, even in those with stable courses.
Article
Medicine, Research & Experimental
Jennifer McAdow, Shuo Yang, Tiffany Ou, Gary Huang, Matthew B. Dobbs, Christina A. Gurnett, Michael J. Greenberg, Aaron N. Johnson
Summary: Nemaline myopathy, as well as other musculoskeletal disorders, is caused by pathogenic variants in the Tropomyosin 2 gene, leading to muscle development and function issues. Through experiments in Drosophila, mice, and zebrafish models, the pathomechanisms of several TPM2 variants were revealed, and it was found that these variants can cause musculoskeletal defects. These assays suggest that our myogenic experiments can predict the clinical severity of TPM2 variants.
Review
Biochemistry & Molecular Biology
Patrizia Bottoni, Giulia Gionta, Roberto Scatena
Summary: Mitochondrial myopathies are a heterogeneous group of diseases caused by genetic mutations in proteins involved in mitochondrial oxidative metabolism. These myopathies show significant differences in their evolution, but some physiological and pathophysiological aspects of mitochondria reveal other potential molecular mechanisms that may play a significant role in their clinical progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Daniel Natera-de Benito, Carlos Ortez, Cristina Jou, Cecilia Jimenez-Mallebrera, Anna Codina, Laura Carrera-Garcia, Jessica Exposito-Escudero, Sergi Cesar, Loreto Martorell, Pia Gallano, Lidia Gonzalez-Quereda, Daniel Cuadras, Jaume Colomer, Delia Yubero, Francesc Palau, Andres Nascimento
Summary: Congenital myopathies are a genetically and clinically heterogeneous group of muscular disorders, with fibrosis and fatty replacement in muscle tissue being associated with clinical severity. Mutations in TTN are responsible for a higher proportion of cases than previously thought, indicating their significant role in the pathology of the disease.
PEDIATRIC NEUROLOGY
(2021)
Article
Genetics & Heredity
Francisco Cammarata-Scalisi, Michele Callea, Diego Martinelli, Colin Eric Willoughby, Antonio Cardenas Tadich, Maykol Araya Castillo, Maria Angelina Lacruz-Rengel, Marco Medina, Piercesare Grimaldi, Enrico Bertini, Julian Nevado
Summary: Phelan-McDermid syndrome is a rare and complex neurodevelopmental disorder caused by microdeletion or mutations in the SHANK3 gene on chromosome 22. The clinical presentation is variable, and diagnosis requires genetic analysis and multidisciplinary care.
Editorial Material
Genetics & Heredity
Francesco Nicita, Lorena Travaglini, Francesco Bombelli, Michele Tosi, Stefano Pro, Enrico Bertini, Adele D'Amico
Summary: This study reports a novel association between pathogenic variants in the SEPSECS gene and complex movement disorder with thin corpus callosum. Clinical exome sequencing revealed two missense variants. The case represents an early-onset pyramidal syndrome with optic nerve hypoplasia that slowly evolved into extrapyramidal syndrome featuring dystonia-parkinsonism, associated with thin corpus callosum.
NEUROLOGY-GENETICS
(2022)
Article
Genetics & Heredity
Salvatore Rossi, Anna Rubegni, Vittorio Riso, Melissa Barghigiani, Maria Teresa Bassi, Roberta Battini, Enrico Bertini, Cristina Cereda, Ettore Cioffi, Chiara Criscuolo, Beatrice Dal Fabbro, Clemente Dato, Maria Grazia D'Angelo, Antonio Di Muzio, Luca Diamanti, Maria Teresa Dotti, Alessandro Filla, Valeria Gioiosa, Rocco Liguori, Andrea Martinuzzi, Roberto Massa, Andrea Mignarri, Rossana Moroni, Olimpia Musumeci, Francesco Nicita, Ilaria Orologio, Laura Orsi, Elena Pegoraro, Antonio Petrucci, Massimo Plumari, Ivana Ricca, Giovanni Rizzo, Silvia Romano, Roberto Rumore, Simone Sampaolo, Marina Scarlato, Marco Seri, Cristina Stefan, Giulia Straccia, Alessandra Tessa, Lorena Travaglini, Rosanna Trovato, Lucia Ulgheri, Giovanni Vazza, Antonio Orlacchio, Gabriella Silvestri, Filippo Maria Santorelli, Mariarosa Anna Beatrice Melone, Carlo Casali
Summary: This study presents clinical and molecular findings of a large cohort of Italian patients with SPAST-HSP. The patients primarily displayed spastic gait, and some patients also had complications such as intellectual disability, polyneuropathy, and cognitive decline. Male patients showed more severe symptoms of spastic paraplegia.
NEUROLOGY-GENETICS
(2022)
Article
Clinical Neurology
Matthew N. Bainbridge, Aloran Mazumder, Daisuke Ogasawara, Rami Abou Jamra, Genevieve Bernard, Enrico Bertini, Lydie Burglen, Heidi Cope, Ali Crawford, Alexa Derksen, Leon Dure, Emily Gantz, Margarete Koch-Hogrebe, Anna C. E. Hurst, Sonal Mahida, Paige Marshall, Alessia Micalizzi, Antonio Novelli, Hongfan Peng, Diana Rodriguez, Shira L. Robbins, S. Lane Rutledge, Roberta Scalise, Sophia Schliesske, Vandana Shashi, Siddharth Srivastava, Isabella Thiffault, Sarah Topol, Leila Qebibo, Dagmar Wieczorek, Benjamin Cravatt, Svasti Haricharan, Ali Torkamani, Jennifer Friedman
Summary: Mutation of the endocannabinoid gene DAGLA causes a pediatric syndrome characterized by developmental delay, ataxia, and abnormal head and eye movements. The truncated protein may be mislocalized, leading to the observed phenotype. This study highlights the first direct link between an endocannabinoid system component and human genetic disease.
Article
Biochemistry & Molecular Biology
Romina Romaniello, Ludovica Pasca, Elena Panzeri, Fulvio D'Abrusco, Lorena Travaglini, Valentina Serpieri, Sabrina Signorini, Chiara Aiello, Enrico Bertini, Maria Teresa Bassi, Enza Maria Valente, Ginevra Zanni, Renato Borgatti, Filippo Arrigoni
Summary: Pathogenic variants in the ITPR1 gene are associated with autosomal dominant spinocerebellar ataxia. Superior vermian and hemispheric cerebellar atrophy on MRI can be a distinguishing feature of ITPR1-related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Fiorella Colasuonno, Chiara Marioli, Marco Tartaglia, Enrico Bertini, Claudia Compagnucci, Sandra Moreno
Summary: Riboflavin transporter deficiency (RTD) is a rare genetic disorder characterized by insufficient supply of riboflavin and impairment of metabolic pathways. Recent studies have shown a connection between cellular energy dysmetabolism, cytoskeletal derangement, and RTD. Patient specific RTD models using induced pluripotent stem cells have provided evidence of redox imbalance and cytoskeletal perturbation. These insights may lead to custom therapeutic strategies for patients unresponsive to high-dose riboflavin treatments.
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)
Review
Biochemistry & Molecular Biology
Riccardo Zocchi, Claudia Compagnucci, Enrico Bertini, Antonella Sferra
Summary: Microtubules (MTs) are dynamic components of the cell cytoskeleton with diverse functions. The tubulin code, which is generated by tubulin gene products and post-translational modifications, regulates MT behavior and functions through protein effectors. Understanding the molecular mechanisms of the tubulin code is crucial for deciphering neurodegenerative disorders and neural processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Georgia Stimpson, Danielle Ramsey, Amy Wolfe, Anna Mayhew, Mariacristina Scoto, Giovanni Baranello, Robert Muni Lofra, Marion Main, Evelin Milev, Giorgia Coratti, Marika Pane, Valeria Sansone, Adele D'Amico, Enrico Bertini, Sonia Messina, Claudio Bruno, Emilio Albamonte, Elena Stacy Mazzone, Jacqueline Montes, Allan M. Glanzman, Zarazuela Zolkipli-Cunningham, Amy Pasternak, Tina Duong, Sally Dunaway Young, Matthew Civitello, Chiara Marini-Bettolo, John W. Day, Basil T. Darras, Darryl C. De Vivo, Richard S. Finkel, Eugenio Mercuri, Francesco Muntoni
Summary: The study investigates the motor function of participants with Spinal Muscular Atrophy (SMA) using the Revised Hammersmith Scale (RHS), and contextualizes the findings with the Hammersmith Functional Motor Scale-Expanded (HFMSE). The transitional group, including crawlers, standers, and walkers-with-assistance, shows the most significant decline in the RHS score over a year. The study highlights the importance of considering SMA type, motor function, and baseline RHS score in interpreting the change scores.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pediatrics
Claudia Brogna, Marika Pane, Giorgia Coratti, Adele D'Amico, Elena Pegoraro, Luca Bello, Valeria Ada Maria Sansone, Emilio Albamonte, Sonia Messina, Antonella Pini, Maria Grazia D'Angelo, Claudio Bruno, Tiziana Mongini, Federica Silvia Ricci, Angela Berardinelli, Roberta Battini, Riccardo Masson, Enrico Silvio Bertini, Luisa Politano, Eugenio Mercuri
Summary: This study evaluated the impact of exon skipping mutations in DMD patients, finding that PUL 2.0 can detect changes in upper limb function. Patients amenable to skipping exon 44 had smaller changes, while those amenable to skipping exon 53 had larger changes. These findings are helpful in designing clinical trials and interpreting real-world data in non-ambulant patients.
Article
Clinical Neurology
Thomas J. Crawford, Kathryn C. Swoboda, Darryl De Vivo, Enrico Bertini, Wuh-Liang S. Hwu, Richard Finkel, Janbernd L. Kirschner, Nancy Kuntz, Aledie Navas A. Nazario, Julie Parsons, Astrid M. Pechmann, M. Monique M. J. Ryan, Russell Butterfield, Haluk Topaloglu, Tawfeg A. Ben-Omran, Valeria Sansone, Yuh-Jyh Jong, Francy Shu, Cong Zhu, Stephanie R. Raynaud, Tiffany D. Lago, Angela Paradis, Richard Foster, Russell Chin, Zdenek Berger, NURTURE Study Grp
Summary: The NURTURE study provides evidence for the effectiveness and safety of early treatment with nusinersen in children with presymptomatic spinal muscular atrophy. The results demonstrate the durability of treatment effects and the potential for improved outcomes in motor function and survival.
Article
Neurosciences
Vito Luigi Colona, Enrico Bertini, Maria Cristina Digilio, Adele D'Amico, Antonio Novelli, Stefano Pro, Elisa Pisaneschi, Francesco Nicita
Summary: POLR3B gene encodes the RPC2 subunit of RNA polymerase III, and pathogenic variants are associated with various disorders, including hypomyelinating leukodystrophy and Charcot-Marie-Tooth syndrome type 1I. In this study, a new variant in the POLR3B gene was identified in a patient with developmental delay, epilepsy, and polyneuropathy.
Article
Genetics & Heredity
Aurelien Perrin, Corinne Metay, Marco Savarese, Rabah Ben Yaou, German Demidov, Isabelle Nelson, Guilhem Sole, Yann Pereon, Enrico Silvio Bertini, Fabiana Fattori, Adele D'Amico, Federica Ricci, Mira Ginsberg, Andreea Seferian, Odile Boespflug-Tanguy, Laurent Servais, Francoise Chapon, Emmeline Lagrange, Karen Gaudon, Adrien Bloch, Robin Ghanem, Lucie Guyant-Marechal, Mridul Johari, Charles Van Goethem, Michel Fardeau, Raul Juntas Morales, Casie A. Genetti, Minttu Marttila, Michel Koenig, Alan Beggs, Bjarne Udd, Gisele Bonne, Mireille Cossee
Summary: Titinopathies are complex neuromuscular pathologies caused by mutations in the titin gene (TTN). A study identified multiple deletion-type CNVs in the TTN gene in several families, revealing new genotype-phenotype associations, mainly distal myopathy.
JOURNAL OF MEDICAL GENETICS
(2023)
