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
Genetics & Heredity
Julia Whittle, Aaron Johnson, Matthew B. Dobbs, Christina A. Gurnett
Summary: Distal arthrogryposis and lethal congenital contracture syndromes are a group of disorders characterized by congenital limb contractures, with diverse but overlapping underlying mechanisms. Insights into these genetic diseases have been gained through in vitro molecular studies and in vivo models in fruit fly, zebrafish, and mice.
Review
Orthopedics
Jacques Griffet, Klaus Dieterich, Veronique Bourg, Emeline Bourgeois
Summary: Arthrogryposis multiplex congenita (AMC) is characterized by congenital joint contractures affecting at least two joints, with two distinct types requiring different treatment approaches. The goal for patients with AMC is to achieve functional mobility, rather than maximal range of motion.
ORTHOPAEDICS & TRAUMATOLOGY-SURGERY & RESEARCH
(2021)
Article
Medicine, General & Internal
Silvina Noemi Contreras-Capetillo, Jose Rafael Palma-Baquedano, Nina Valadez-Gonzalez, Pablo Manrique-Saide, Hirian Alonso Moshe Barrera-Perez, Doris Pinto-Escalante, Norma Pavia-Ruz
Summary: The article reports a Zika positive patient with a sequence of fetal brain disruption, arthrogryposis, and absence of the distal third of the right forearm. This case expands clinical observations of congenital Zika syndrome and may be related to disruptive vascular events.
FRONTIERS IN MEDICINE
(2021)
Article
Genetics & Heredity
Gozde Tutku Turgut, Umut Altunoglu, Tugba Sarac Sivrikoz, Guven Toksoy, Tugba Kalayci, Sahin Avci, Birsen Karaman, Cagri Gulec, Seher Basaran, Gozde Yesil Sayin, Hulya Kayserili, Zehra Oya Uyguner
Summary: Multiple congenital contractures (MCC) is a rare non-progressive condition caused by genetic defects in various body systems. This study identifies USP14 as a gene associated with MCC, with symptoms including callosal anomalies, muscle wasting, and early lethality.
Article
Clinical Neurology
Karlijn Bouman, Benno Kusters, Josine M. De Winter, Cynthia Gillet, Esmee S. B. Van Kleef, Lilian Eshuis, Guy Brochier, Angeline Madelaine, Clemence Labasse, Claire Boulogne, Baziel G. M. Van Engelen, Coen A. C. Ottenheijm, Norma B. Romero, Nicol C. Voermans, Edoardo Malfatti
Summary: Patients with NEM6 exhibit characteristic pathological features in muscle tissue, including ring-rods fibers and central cores. Pathologically, there is also nuclear clumping, overexpression of titin, and granulofilamentous protein material, which may be the histopathologic epiphenomenon of altered interaction between mutated KBTBD13 protein and thin filaments.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Neurosciences
Clemence Labasse, Guy Brochier, Ana-Lia Taratuto, Bruno Cadot, John Rendu, Soledad Monges, Valerie Biancalana, Susana Quijano-Roy, Mai Thao Bui, Anais Chanut, Angeline Madelaine, Emmanuelle Lacene, Maud Beuvin, Helge Amthor, Laurent Servais, Yvan de Feraudy, Marcela Erro, Maria Saccoliti, Osorio Abath Neto, Julien Faure, Beatrice Lannes, Vincent Laugel, Sandra Coppens, Fabiana Lubieniecki, Ana Buj Bello, Nigel Laing, Teresinha Evangelista, Jocelyn Laporte, Johann Bohm, Norma B. Romero
Summary: This study expands the genetic and morphological spectrum of severe ACTA1-related nemaline myopathy, highlights the enlargement of the perinuclear space as an ultrastructural hallmark, and indicates a potential genotype/phenotype correlation.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Article
Neurosciences
Stefan Nicolau, Aneesha Dasgupta, Surendra Dasari, M. Cristine Charlesworth, Kenneth L. Johnson, Akhilesh Pandey, Jason D. Doles, Margherita Milone
Summary: Acquired sporadic late onset nemaline myopathy (SLONM) and inherited nemaline myopathy (iNM) both involve the accumulation of nemaline rods in muscle fibers. However, SLONM can be treated while iNM cannot. The distinction between these disorders is crucial for accurate diagnosis and the development of effective treatments. Through histological, proteomic, and transcriptomic analysis, we identified unique pathological and molecular signatures associated with SLONM and iNM, suggesting different underlying mechanisms. These findings provide valuable insights for enhancing diagnostic tools and developing treatments for SLONM.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Juliana Gurgel-Giannetti, Lucas Santos Souza, Guilherme L. Yamamoto, Marina Belisario, Monize Lazar, Wilson Campos, Rita de Cassia M. Pavanello, Mayana Zatz, Umbertina Reed, Edmar Zanoteli, Acary Bulle Oliveira, Vilma-Lotta Lehtokari, Erasmo B. Casella, Marcela C. Machado-Costa, Carina Wallgren-Pettersson, Nigel G. Laing, Vincenzo Nigro, Mariz Vainzof
Summary: Nemaline myopathy in Brazilian patients shows significant clinical and genetic heterogeneity, with a high frequency of NEB gene mutations. There is noticeable variability in clinical presentation and MRI patterns, with respiratory involvement often being severe.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Sarah MacKenzie Picker, George Parker, Paul Gissen
Summary: Congenital arthrogryposis (CA) is characterized by multiple contractures present at birth, with collagen disorders being a notable cause. This review aims to identify common features, genotype-phenotype correlations, and potential treatment options for CA caused by collagen structure and function abnormalities. Nine genes associated with five clinical phenotypes were identified, with extreme variability in phenotype. Current postnatal surgical correction is the main treatment, but in-utero therapies and splice correction therapies are being developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pediatrics
Dongmei Liu, Jiali Yu, Xin Wang, Yang Yang, Li Yu, Shi Zeng, Ming Zhang, Ganqiong Xu
Summary: This study reports a case of fetal nemaline myopathy (NM) caused by a KLHL40 gene variation, resulting in arthrogryposis multiplex congenita (AMC). Ultrasonography and histopathological results showed enhanced echo intensity and decreased muscle thickness, providing early clues for prenatal diagnosis of NM. Additionally, this article is the first to describe a case of NM associated with complex congenital heart disease (CHD).
FRONTIERS IN PEDIATRICS
(2022)
Article
Genetics & Heredity
Cristina Skrypnyk, Aseel Ahmed Husain, Hisham Y. Hassan, Jameel Ahmed, Abdulla Darwish, Latifa Almusalam, Noureddine Ben Khalaf, Fahad Al Qashar
Summary: This study reports two Arab patients from consanguineous families diagnosed with different severities of nemaline myopathy. The clinical phenotype was linked to homozygous variants in NEB and KLHL40 genes. The study highlights the importance of detailed assessment in prenatal, neonatal, and infancy stages for accurate diagnosis and intervention of nemaline myopathy.
FRONTIERS IN GENETICS
(2023)
Article
Genetics & Heredity
Felix Boschann, Muhsin O. Cogulu, Davut Pehlivan, Saranya Balachandran, Pedro Vallecillo-Garcia, Christopher M. Grochowski, Nils R. Hansmeier, Zeynep H. Coban Akdemir, Cesar A. Prada-Medina, Ayca Aykut, Bjorn Fischer-Zirnsak, Simon Badura, Burak Durmaz, Ferda Ozkinay, Rene Haegerling, Jennifer E. Posey, Sigmar Stricker, Gabriele Gillessen-Kaesbach, Malte Spielmann, Denise Horn, Knut Brockmann, James R. Lupski, Uwe Kornak, Julia Schmidt
Summary: This study aimed to identify the genetic cause of a novel form of distal arthrogryposis through genomics analysis. The researchers discovered that rare biallelic recessive trait variants in the ADAMTS15 gene were associated with distal arthrogryposis syndrome.
GENETICS IN MEDICINE
(2022)
Article
Neurosciences
Nicolas N. Madigan, Michael J. Polzin, Gaofeng Cui, Teerin Liewluck, Mohammad H. Alsharabati, Christopher J. Klein, Anthony J. Windebank, Georges Mer, Margherita Milone
Summary: Pathogenic variants in the MYH2 gene can lead to MYH2-myopathy, characterized by ophthalmoparesis and proximal weakness. The pathological features include loss and atrophy of type 2A fibers, along with rimmed vacuoles, nemaline rods, and other abnormalities. This study reports a novel myopathological phenotype with large myofilamentous tangles and nemaline rods in addition to previously reported features.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Genetics & Heredity
Daniel Natera-de Benito, Julie A. Jurgens, Alison Yeung, Irina T. Zaharieva, Adnan Manzur, Stephanie P. DiTroia, Silvio Alessandro Di Gioia, Lynn Pais, Veronica Pini, Brenda J. Barry, Wai-Man Chan, James E. Elder, John Christodoulou, Eleanor Hay, Eleina M. England, Pinki Munot, David G. Hunter, Lucy Feng, Danielle Ledoux, Anne O'Donnell-Luria, Rahul Phadke, Elizabeth C. Engle, Anna Sarkozy, Francesco Muntoni
Summary: This study describes five patients with recessive missense and splice site variants in the COL25A1 gene, presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without ocular congenital cranial dysinnervation. The clinical features of the older patients remained stable over time, without involvement of the central nervous system. This research extends the phenotypic and genotypic spectrum of COL25A1 related conditions and contributes to our understanding of the complex process of intramuscular motor innervation.
Article
Clinical Neurology
Monica Llano-Diez, Carlos Ignacio Ortez, Judit Armas Gay, Lidia Alvarez-Cabado, Cristina Jou, Julita Medina, Andres Nascimento, Cecilia Jimenez-Mallebrera
NEUROMUSCULAR DISORDERS
(2017)
Article
Clinical Neurology
Ana Fernandez-Marmiesse, M. Carmen Carrascosa-Romero, Blanca Alfaro Ponce, Andres Nascimento, Carlos Ortez, Norma Romero, Lourdes Palacios, Cecilia Jimenez-Mallebrera, Cristina Jou, Sofia Gouveia, Maria L. Couce
NEUROMUSCULAR DISORDERS
(2017)
Article
Medicine, Research & Experimental
Kyle Thompson, Nicole Mai, Monika Olahova, Filippo Scialo, Luke E. Formosa, David A. Stroud, Madeleine Garrett, Nichola Z. Lax, Fiona M. Robertson, Cristina Jou, Andres Nascimento, Carlos Ortez, Cecilia Jimenez-Mallebrera, Steven A. Hardy, Langping He, Garry K. Brown, Paula Marttinen, Robert McFarland, Alberto Sanz, Brendan J. Battersby, Penelope E. Bonnen, Michael T. Ryan, Zofia M. A. Chrzanowska-Lightowlers, Robert N. Lightowlers, Robert W. Taylor
EMBO MOLECULAR MEDICINE
(2018)
Article
Medicine, General & Internal
Cristina Jou, Juan D. Ortigoza-Escobar, Maria M. Ocallaghan, Andres Nascimento, Alejandra Darling, Leticia Pias-Peleteiro, Belen Perez-Duenas, Mercedes Pineda, Anna Codina, Cesar Arjona, Judith Armstrong, Francesc Palau, Antonia Ribes, Laura Gort, Frederic Tort, Placido Navas, Eduardo Ruiz-Pesini, Sonia Emperador, Ester Lopez-Gallardo, Pilar Bayona-Bafaluy, Raquel Montero, Cecilia Jimenez-Mallebrera, Angels Garcia-Cazorla, Julio Montoya, Delia Yubero, Rafael Artuch
JOURNAL OF CLINICAL MEDICINE
(2019)
Article
Genetics & Heredity
Laura Carrera-Garcia, Daniel Natera-de Benito, Klaus Dieterich, Marta G. G. de la Banda, Adrien Felter, Emili Inarejos, Anna Codina, Cristina Jou, Monica Roldan, Francesc Palau, Janet Hoenicka, Jordi Pijuan, Carlos Ortez, Jessica Exposito-Escudero, Chantal Durand, Frederique Nugues, Cecilia Jimenez-Mallebrera, Jaume Colonner, Robert Y. Carlier, Hanns Loechmueller, Susana Quijano-Roy, Andres Nascimento
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2019)
Article
Cell Biology
Daniela Stanga, Qingchuan Zhao, Miroslav P. Milev, Djenann Saint-Dic, Cecilia Jimenez-Mallebrera, Michael Sacher
Article
Clinical Neurology
Cristina Dominguez-Gonzalez, Marcos Madruga-Garrido, Fabiola Mavillard, Caterina Garone, Francisco Javier Aguirre-Rodriguez, M. Alice Donati, Karin Kleinsteuber, Itxaso Marti, Elena Martin-Hernandez, Juan P. Morealejo-Aycinena, Francina Munell, Andres Nascimento, Susana G. Kalko, M. Dolores Sardina, Concepcion Alvarez del Vayo, Olga Serrano, Yuelin Long, Yuqi Tu, Bruce Levin, John L. P. Thompson, Kristen Engelstad, Jasim Uddin, Javier Torres-Torronteras, Cecilia Jimenez-Mallebrera, Ramon Marti, Carmen Paradas, Michio Hirano
ANNALS OF NEUROLOGY
(2019)
Review
Genetics & Heredity
Cristina Dominguez-Gonzalez, Aurelio Hernandez-Lain, Eloy Rivas, Ana Hernandez-Voth, Javier Sayas Catalan, Roberto Fernandez-Torron, Carmen Fuiza-Luces, Jorge Garcia Garcia, German Moris, Montse Olive, Frances Miralles, Jordi Diaz-Manera, Candela Caballero, Bosco Mendez-Ferrer, Ramon Marti, Elena Garcia Arumi, Maria Carmen Badosa, Jesus Esteban, Cecilia Jimenez-Mallebrera, Alberto Blazquez Encinar, Joaquin Arenas, Michio Hirano, Miguel Angel Martin, Carmen Paradas
ORPHANET JOURNAL OF RARE DISEASES
(2019)
Article
Endocrinology & Metabolism
Nadja Mingirulli, Angela Pyle, Denisa Hathazi, Charlotte L. Alston, Nicolai Kohlschmidt, Gina O'Grady, Leigh Waddell, Frances Evesson, Sandra B. T. Cooper, Christian Turner, Jennifer Duff, Ana Topf, Delia Yubero, Cristina Jou, Andres Nascimento, Carlos Ortez, Angels Garcia-Cazorla, Claudia Gross, Maria O'Callaghan, Saikat Santra, Maryanne A. Preece, Michael Champion, Sergei Korenev, Efsthatia Chronopoulou, Majumdar Anirban, Germaine Pierre, Daniel McArthur, Kyle Thompson, Placido Navas, Antonia Ribes, Frederic Tort, Agatha Schluter, Aurora Pujol, Raquel Montero, Georgia Sarquella, Hanns Lochmueller, Cecilia Jimenez-Mallebrera, Robert W. Taylor, Rafael Artuch, Janbernd Kirschner, Sarah C. Gruenert, Andreas Roos, Rita Horvath
JOURNAL OF INHERITED METABOLIC DISEASE
(2020)
Article
Multidisciplinary Sciences
Miroslav P. Milev, Daniela Stanga, Anne Schaenzer, Andres Nascimento, Djenann Saint-Dic, Carlos Ortez, Daniel Natera-de Benito, Desire Gonzalez Barrios, Jaume Colomer, Carmen Badosa, Cristina Jou, Pia Gallano, Lidia Gonzalez-Quereda, Ana Topf, Katherine Johnson, Volker Straub, Andreas Hahn, Michael Sacher, Cecilia Jimenez-Mallebrera
SCIENTIFIC REPORTS
(2019)
Letter
Clinical Neurology
Cecilia Jimenez-Mallebrera
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Enrico Castroflorio, Ana Joaquina Perez Berna, Aristides Lopez-Marquez, Carmen Badosa, Pablo Loza-Alvarez, Monica Roldan, Cecilia Jimenez-Mallebrera
Summary: This study reveals the inability of patient-derived fibroblasts to build the extracellular collagen VI network and its correlation with increased phosphorylation of the collagen VI receptor CMG2, leading to the accumulation of endosomes and lysosomes. Using gene-editing tools, the researchers were able to rescue the normal extracellular network and restore the homeostasis of endosomes and lysosomes. These findings uncover a previously unknown role of CMG2 in regulating intracellular environment and its implication in collagen VI-related muscular dystrophy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Cristina Jou, Andres Nascimento, Anna Codina, Julio Montoya, Ester Lopez-Gallardo, Sonia Emperador, Eduardo Ruiz-Pesini, Raquel Montero, Daniel Natera-de Benito, Carlos Ortez, Jesus Marquez, Maria Zelaya, Alfonso Gutierrez-Mata, Carmen Badosa, Laura Carrera-Garcia, Jesica Exposito-Escudero, Monica Roldan, Yolanda Camara, Ramon Marti, Isidre Ferrer, Cecilia Jimenez-Mallebrera, Rafael Artuch
Summary: Thymidine kinase (TK2) deficiency in pediatric patients leads to mitochondrial DNA depletion syndrome. This study examines the clinical, biochemical, genetic, histopathological, and ultrastructural features of a group of pediatric patients with TK2 deficiency. Muscle biopsies show ragged red fibers in all patients, with a higher prevalence in younger patients. Inflammatory infiltrates and overexpression of MHC I are observed in younger patients. Ultrastructural analysis reveals concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles as major mitochondrial alterations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Medicine, Research & Experimental
Veronique Bolduc, A. Reghan Foley, Herimela Solomon-Degefa, Apurva Sarathy, Sandra Donkervoort, Ying Hu, Grace S. Chen, Katherine Sizov, Matthew Nalls, Haiyan Zhou, Sara Aguti, Beryl B. Cummings, Monkol Lek, Taru Tukiainen, Jamie L. Marshall, Oded Regev, Dina Marek-Yagel, Anna Sarkozy, Russell J. Butterfield, Cristina Jou, Cecilia Jimenez-Mallebrera, Yan Li, Corine Gartioux, Kamel Mamchaoui, Valerie Allamand, Francesca Gualandi, Alessandra Ferlini, Eric Hanssen, Steve D. Wilton, Shireen R. Lamande, Daniel G. MacArthur, Raimund Wagener, Francesco Muntoni, Carsten G. Bonnemann