Article
Clinical Neurology
Jan Brands, Frank Steffen, Jochen Spennes, Tosso Leeb, Thomas Bilzer
Summary: This study describes analogous clinical signs and histopathological alterations in Landseer dogs, showing that these affected dogs can serve as a valuable animal model for human Ullrich congenital muscular dystrophy.
Article
Biochemistry & Molecular Biology
Karim Naghipoor, Teymoor Khosravi, Morteza Oladnabi
Summary: Mutations in the COL12A1 gene have been found to be associated with the onset of congenital Ullrich muscular dystrophy 2 (UCMD2) and Bethlem myopathy. The severity of symptoms depends on the type and homozygosity of the mutation. This study identified a novel homozygous missense variant in COL12A1 in a nine-year-old Iranian patient, confirming its role in the development of UCMD2. Genetic testing for this mutation may be useful in diagnosing patients with this disease.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Cell & Tissue Engineering
Nana Takenaka-Ninagawa, Jinsol Kim, Mingming Zhao, Masae Sato, Tatsuya Jonouchi, Megumi Goto, Clemence Kiho Bourgeois Yoshioka, Rukia Ikeda, Aya Harada, Takahiko Sato, Makoto Ikeya, Akiyoshi Uezumi, Masashi Nakatani, Satoru Noguchi, Hidetoshi Sakurai
Summary: This study demonstrates that COL6 supplementation improves muscle regeneration and maturation in UCMD model mice.
STEM CELL RESEARCH & THERAPY
(2021)
Article
Medicine, General & Internal
Jun Hu, Yan-Hui Chen, Xin Fang, Yu Zhou, Feng Chen
Summary: This study presents a Chinese family with UCMD caused by compound heterozygous mutations of the COL6A2 gene. Genetic counseling and prenatal diagnosis played a crucial role in helping the family make informed decisions. The identification of COL6A2 mutations allowed for voluntary interruption of a UCMD-affected pregnancy.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Dermatology
Alexandra M. Ritter, Lara Wine Lee
Summary: This case report highlights the importance of including cutaneous findings, such as keratosis pilaris, when evaluating patients with syndromic features. The patient, diagnosed with Ullrich congenital muscular dystrophy, presented with severe keratosis pilaris, hypotonia, and velvety skin on the palms and soles.
PEDIATRIC DERMATOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Alberto Di Martino, Matilde Cescon, Claudio D'Agostino, Francesco Schilardi, Patrizia Sabatelli, Luciano Merlini, Cesare Faldini
Summary: Collagen VI has diverse functions in tissues, including mechanical roles, cytoprotective functions, and regulation of cell differentiation and autophagy. Mutations in COL6A1, COL6A2, and COL6A3 genes cause muscular disorders such as UCMD, BM, and MM, which present with muscle wasting and weakness, joint contractures, and respiratory compromise. Currently, effective therapeutic strategies are lacking, and the effects of collagen VI mutations on other tissues are poorly understood. This review aims to outline the role of collagen VI in the musculoskeletal system and provide an update on its tissue-specific functions to bridge the knowledge gap between scientists and clinicians managing collagen VI-related myopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Genetics & Heredity
Pitcha Chompoopong, Margherita Milone
Summary: GDP-mannose pyrophosphorylase B (GMPPB) is a cytoplasmic protein that catalyzes the formation of GDP-mannose. Impaired GMPPB function leads to alpha-dystroglycan (alpha-DG) disruptions, causing dystroglycanopathy. GMPPB-related disorders are inherited in an autosomal recessive manner and can manifest as severe congenital muscular dystrophy (CMD), limb-girdle muscular dystrophy (LGMD), or recurrent rhabdomyolysis. Mutations in GMPPB can also affect neuromuscular transmission and cause congenital myasthenic syndrome. The unique feature of GMPPB-related disorders is the impairment of neuromuscular transmission.
Article
Genetics & Heredity
Van Khanh Tran, Ngoc-Lan Nguyen, Lan Ngoc Thi Tran, Phuong Thi Le, Anh Hai Tran, Tuan L. A. Pham, Nguyen Thi Kim Lien, Nguyen Thi Xuan, Le Tat Thanh, Thanh Van Ta, Thinh Huy Tran, Huy-Hoang Nguyen
Summary: This study identified seven pathogenic/likely pathogenic variants in the LAMA2 gene in six patients with congenital muscular dystrophy from five unrelated Vietnamese families, providing genetic etiology and counseling for their parents.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
P. A. Chausova, O. P. Ryzhkova, G. E. Rudenskaya, V. B. Chernykh, O. A. Shchagina, A. V. Polyakov
Summary: Merosine deficient congenital muscular dystrophy is a common form of muscular dystrophy caused by a genetic deficiency. New variants with this type of inheritance may be hidden in the genetic makeup of parents.
FRONTIERS IN GENETICS
(2021)
Article
Clinical Neurology
Nirmala Dushyanthi Sirisena, U. M. Jayami Eshana Samaranayake, Osorio Lopes Abath Neto, A. Reghan Foley, B. A. P. Sajeewani Pathirana, Nilaksha Neththikumara, C. Sampath Paththinige, Pyara Rathnayake, Sandra Donkervoort, Carsten G. Bonnemann, Vajira H. W. Dissanayake
Summary: Collagen VI-related dystrophies are a type of congenital muscular dystrophy caused by pathogenic variants in COL6A1, COL6A2 or COL6A3 genes. This study reports a consanguineous Sri Lankan family with two children affected by UCMD due to a novel variant in the COL6A1 gene. The findings contribute to the understanding of genotype-phenotype correlations in UCMD.
Article
Biochemistry & Molecular Biology
Benjamin E. Hinz, Sydney G. Walker, Austin Xiong, Rose A. Gogal, Michael J. Schnieders, Lori L. Wallrath
Summary: Mutations in the LMNA gene cause laminopathies, with different amino acid substitutions leading to distinct diseases in Lamin A/C. The nature of the amino acid replacement may dictate disease severity and pathogenicity. In silico analyses suggest potential genotype-phenotype connections in laminopathies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Patrizia Sabatelli, Luciano Merlini, Alberto Di Martino, Vittoria Cenni, Cesare Faldini
Summary: Ullrich congenital muscular dystrophy (UCMD) is a severe form of muscular dystrophy characterized by abnormal fat substitution in the periphery of muscles and increased interstitial cells. The muscle biopsy study revealed the unique pattern of muscle degeneration and the potential involvement of interstitial structures.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2022)
Article
Multidisciplinary Sciences
Pedro Gameiro dos Santos, Ana Rita Soares, Solveig Thorsteinsdottir, Gabriela Rodrigues
Summary: The extracellular matrix (ECM) is important for cell structure and signaling. Traditional 2D cell culture models cannot accurately represent in vivo processes. Deficiencies in ECM composition and cell-ECM interactions contribute to various diseases.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Multidisciplinary Sciences
Pedro Gameiro dos Santos, Ana Rita Soares, Solveig Thorsteinsdottir, Gabriela Rodrigues
Summary: The extracellular matrix (ECM) is important for cell structure and signaling. Two-dimensional cell culture models oversimplify cell-ECM interactions, while deficiencies in ECM and cell-ECM interactions contribute to disease progression.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Article
Clinical Neurology
Maria Barington, Morten Duno, Ulf Birkedal, John Vissing, Alfred Peter Born, Thomas Krag, Elsebet ostergaard
Summary: The three major collagen VI genes (COL6A1, COL6A2, and COL6A3) encode microfibrillar components of the extracellular matrix in various tissues. A pathogenic variant (c.1741-6G > A) in the COL6A1 gene was identified in three patients with severe Ullrich congenital muscular dystrophy. The variant induces aberrant splicing, leading to loss of collagen VI function and impaired secretion. This finding expands our understanding of pathogenic variants causing Ullrich congenital muscular dystrophy.
NEUROMUSCULAR DISORDERS
(2023)
Article
Clinical Neurology
Katalina Bertran, Oscar Sans Capdevila, Andres Nascimiento, Carlos Ortez, Daniel Natera, Alex Iranzo de Riquer
Summary: This study analyzed the sleep architecture and prevalence of sleep-disordered breathing in patients with type 2 spinal muscular atrophy (SMA) and compared them with age-matched controls. The results showed that SMA type 2 patients had differences in sleep architecture, including decreased total sleep time, increased percentage of stage N1 of NREM sleep, and increased sleep fragmentation due to respiratory related arousals. Existing pediatric sleep questionnaires may not be effective tools for screening sleep-disordered breathing in these patients.
Article
Neurosciences
Jordi Pijuan, Lara Cantarero, Daniel Natera-de Benito, Arola Altimir, Anna Altisent-Huguet, Yaiza Diaz-Osorio, Laura Carrera-Garcia, Jessica Exposito-Escudero, Carlos Ortez, Andres Nascimento, Janet Hoenicka, Francesc Palau
Summary: This study compares the characteristics of mitochondrial dynamics and mitochondria-lysosome axis in different neurogenetic diseases, revealing common and unique cellular phenotypes. It sheds light on the pathophysiological events, new biomarkers, and potential drug targets for these disorders.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Physiology
Laura Brugnara, Ana Isabel Garcia, Serafin Murillo, Josep Ribalta, Guerau Fernandez, Susanna Marquez, Miguel Angel Rodriguez, Maria Vinaixa, Nuria Amigo, Xavier Correig, Susana Kalko, Jaume Pomes, Anna Novials
Summary: The aim of this study was to investigate the relationship between muscle carnosine and type 1 diabetes, as well as how it is influenced by physical activity. The results showed that patients with type 1 diabetes had higher levels of muscle carnosine, which were influenced by physical activity, clinical characteristics, and lipoprotein subfractions.
EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aristides Lopez-Marquez, Matias Morin, Sergio Fernandez-Penalver, Carmen Badosa, Alejandro Hernandez-Delgado, Daniel Natera-de Benito, Carlos Ortez, Andres Nascimento, Daniel Grinberg, Susanna Balcells, Monica Roldan, Miguel Angel Moreno-Pelayo, Cecilia Jimenez-Mallebrera
Summary: Collagen VI-related disorders are a common type of congenital muscular dystrophy without available treatments. This study demonstrates the potential of CRISPR/Cas9-based genome editing to silence or correct pathogenic variants in the COL6A1 gene, leading to a recovery in collagen VI expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Jeffrey M. Statland, Craig Campbell, Urvi Desai, Chafic Karam, Jordi Diaz-Manera, Jeffrey T. Guptill, Lawrence Korngut, Angela Genge, Rabi N. Tawil, Lauren Elman, Nanette C. Joyce, Kathryn R. Wagner, Georgios Manousakis, Anthony A. Amato, Russell J. Butterfield, Perry B. Shieh, Matthew Wicklund, Josep Gamez, Cynthia Bodkin, Alan Pestronk, Conrad C. Weihl, Juan J. Vilchez-Padilla, Nicholas E. Johnson, Katherine D. Mathews, Barry Miller, Ashley Leneus, Marcie Fowler, Marc van de Rijn, Kenneth M. Attie
Summary: This study evaluated the safety and efficacy of ACE-083 in treating FSHD. The results showed that ACE-083 can increase muscle volume, but did not lead to consistent improvements in functional outcomes or patient-reported outcomes.
Article
Genetics & Heredity
Alba Segarra-Casas, Cristina Dominguez-Gonzalez, Aurelio Hernandez-Lain, Maria Teresa Sanchez-Calvin, Ana Camacho, Eloy Rivas, Andrea Campo-Barasoain, Marcos Madruga, Carlos Ortez, Daniel Natera-de Benito, Andres Nascimento, Anna Codina, Maria Jose Rodriguez, Pia Gallano, Lidia Gonzalez-Quereda
Summary: In patients with suspected DMD/BMD who remain genetically undiagnosed after routine genetic testing, mRNA analysis of the DMD gene identified alterations in mRNA level, including deep intronic variants and chromosomal rearrangement, as well as exon skipping events of unclear pathogenicity. These findings highlight the value of mRNA analysis in reaching a precise genetic diagnosis for patients with clinical and anatomopathological suspicion of dystrophinopathy that cannot be diagnosed through routine genetic testing.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Clinical Neurology
Jordi Diaz-Manera, J. Andoni Urtizberea, Carina Schey, Anna Kole, Philipp von Gallwitz, Amy Whiting, Douglas Foerster, Alla Zozulya-Weidenfeller
Summary: Although mexiletine is effective in treating myotonia, supply disruptions in Europe from 2008 to 2018 have caused limited access and awareness of the drug. A mixed-methods, cross-sectional study was conducted to evaluate the consequences and awareness of mexiletine in people with myotonia, revealing poor awareness among general neurologists and significant improvements in myotonia and quality of life for those with access to the drug.
NEUROMUSCULAR DISORDERS
(2023)
Article
Clinical Neurology
Daniel Natera-de Benito, Jonathan Olival, Carla Garcia-Cabau, Cristina Jou, Monica Roldan, Anna Codina, Jessica Exposito-Escudero, Cristina Batlle, Laura Carrera-Garcia, Carlos Ortez, Xavier Salvatella, Francesc Palau, Andres Nascimento, Janet Hoenicka
Summary: A new ANXA11 variant was identified in a patient with severe childhood-onset oculopharyngeal muscular dystrophy. This variant leads to abnormal phase separation and protein aggregation of ANXA11, which affects stress granules dynamics and clearance in fibroblasts. Muscle histopathology confirms the presence of ANXA11 protein aggregates, demonstrating a common pathophysiology for disorders associated with ANXA11 Asp40 allelic variants.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
Andres Nascimento, Christine C. Bruels, Sandra Donkervoort, A. Reghan Foley, Anna Codina, Jose C. Milisenda, Elicia A. Estrella, Chengcheng Li, Jordi Pijuan, Isabelle Draper, Ying Hu, Seth A. Stafki, Lynn S. Pais, Vijay S. Ganesh, Anne O'Donnell-Luria, Safoora B. Syeda, Laura Carrera-Garcia, Jessica Exposito-Escudero, Delia Yubero, Loreto Martorell, Iago Pinal-Fernandez, Hart G. W. Lidov, Andrew L. Mammen, Josep M. Grau-Junyent, Carlos Ortez, Francesc Palau, Partha S. Ghosh, Basil T. Darras, Cristina Jou, Louis M. Kunkel, Janet Hoenicka, Carsten G. Bonnemann, Peter B. Kang, Daniel Natera-de Benito
Summary: This study found that variants in the DTNA gene are associated with human skeletal muscle disease, leading to symptoms such as muscle weakness, fatigue, and exercise intolerance. The study also demonstrated that these variants disrupt the interaction between alpha-dystrobrevin and syntrophin.
ACTA NEUROPATHOLOGICA
(2023)
Article
Biochemistry & Molecular Biology
Anna Codina, Monica Roldan, Daniel Natera-de Benito, Carlos Ortez, Robert Planas, Leslie Matalonga, Daniel Cuadras, Laura Carrera, Jesica Exposito, Jesus Marquez, Cecilia Jimenez-Mallebrera, Josep M. Porta, Andres Nascimento, Cristina Jou
Summary: We developed a method for quantifying dystrophin in DMD and BMD patients using spectral confocal microscopy. The proposed methodology correctly classified patients according to their diagnosis and automated ROI selection. Spectral imaging could be implemented to measure dystrophin expression and pave the way for detailed analysis of its relation to the clinical course. Further studies could be done to understand the expression of dystrophin-associated protein complexes (DAPCs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Maria Justel, Cristina Jou, Andrea Sariego-Jamardo, Natalia Alexandra Julia-Palacios, Carlos Ortez, Maria Luisa Poch, Antonio Hedrera-Fernandez, Hilario Gomez-Martin, Anna Codina, Jana Dominguez-Carral, Jordi Muxart, Aurelio Hernandez-Lain, Sara Vila-Bedmar, Miren Zulaica, Ramon Cancho-Candela, Margarita del Carmen Castro, Alberto de la Osa-langreo, Alfonso Pena-Valenceja, Elena Marcos-Vadillo, Pablo Prieto-Matos, Samuel Ignacio Pascual-Pascual, Adolfo Lopez de Munain, Ana Camacho, Berta Estevez-Arias, Uliana Musokhranova, Mireia Olivella, Alfonso Oyarzabal, Cecilia Jimenez-Mallebrera, Cristina Dominguez-Gonzalez, Andres Nascimento, Angels Garcia-Cazorla, Daniel Natera-de Benito
Summary: This article reports a clinical and histopathological characterization of 25 Roma individuals with LGMD R18 caused by the homozygous TRAPPC11 c.1287+5G>A variant. The variant has functional effects on mitochondrial function, leading to decreased mitochondrial ATP production capacity and alterations in the mitochondrial network architecture. Additionally, microcephaly and clinical decompensation associated with infections are prevalent in individuals with LGMD R18.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Nutrition & Dietetics
Francesc Ribas-Aulinas, Silvia Ribo, Eduard Casas, Marta Mourin-Fernandez, Marta Ramon-Krauel, Ruben Diaz, Carles Lerin, Susana G. G. Kalko, Tanya Vavouri, Josep C. C. Jimenez-Chillaron
Summary: Childhood obesity increases the risk of metabolic dysfunction in adulthood and this dysfunction can be inherited through non-genomic mechanisms. The pathways involved in intergenerational effects of childhood obesity are still unknown. A mouse model of early adiposity was developed by reducing litter size at birth, and the mice from small litters developed obesity and hepatic steatosis. The offspring of these male mice also developed hepatic steatosis, suggesting epigenetic inheritance. Circadian rhythm and lipid metabolic process were found to be highly significant in the liver of these offspring. DNA methylation and small non-coding RNAs were investigated as potential mediators of intergenerational effects, and alterations in sperm DNA methylation and differential expression of certain miRNAs in the testes were observed. These miRNAs may regulate the expression of lipid-related genes in hepatocytes and contribute to the inheritance of hepatic steatosis in this model.
Article
Cell Biology
Sergi Cesar, Oscar Campuzano, Jose Cruzalegui, Victori Fiol, Isaac Moll, Estefania Martinez-Barrios, Irene Zschaeck, Daniel Natera-de Benito, Carlos Ortez, Laura Carrera, Jessica Exposito, Ruben Berrueco, Carles Bautista-Rodriguez, Ivana Dabaj, Marta Gomez Garcia-de-la-Banda, Susana Quijano-Roy, Josep Brugada, Andres Nascimento, Georgia Sarquella-Brugada
Summary: LMNA-related muscular dystrophy is a rare condition that can lead to various laminopathies such as Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B (LGMD1B), and LMNA-related congenital muscular dystrophy (L-CMD). It is associated with heart failure, malignant arrhythmias, and sudden death. This study aimed to comprehensively evaluate the cardiac status of pediatric patients with LMNA-related muscular dystrophy. The results showed that 20% of the patients had malignant arrhythmias, and early-onset EDMD was associated with worse cardiac prognosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Chengcheng Li, Jackson Wilborn, Sara Pittman, Jil Daw, Jorge Alonso-Perez, Jordi Diaz-Manera, Conrad C. Weihl, Gabe Haller
Summary: Genetic testing is crucial for patients with suspected hereditary myopathy, as a significant number of diagnosed myopathy patients carry unknown variants in myopathy genes, leading to a lack of genetic diagnosis. The study focused on limb-girdle muscular dystrophy (LGMD), specifically type R4/2E caused by beta-sarcoglycan (SGCB) mutations. By analyzing the functional impact of missense variants in the SGCB gene, a correlation between variant function and disease severity was discovered, providing valuable insights for clinical interpretation and improving LGMD diagnosis.
JOURNAL OF CLINICAL INVESTIGATION
(2023)