NeurOmics website

NeurOmics website

Integrated European Project on Omics Research of
Rare Neuromuscular and Neurodegenerative Diseases
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      • Ataxia
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      • 1 – Deep phenotype analysis in pre-symptomatic and symptomatic NDD/NMD patients
      • 2 – Identification of novel disease genes in NDD/NMD patients
      • 3 – Identification of modifying factors in cohorts enriched by deep phenotyping
      • 4 – Identification of hypothesis-driven biomarkers for disease progression
      • 5 – Development and implementation of disease group overlapping NGS-based diagnostic panels
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      • 9 – Omics-assisted therapy development
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      • 11 – Modifier gene identification, prioritization and study
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      • Agilent Technologies
      • Ariadne Diagnostics, LLC
      • Bio-Prodict
      • Cambridge University
      • deCODE genetics
      • German Center for Neurodegenerative Diseases (DZNE)
      • Institut National de la Santé et de la Recherche Médicale
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      • Leiden University Medical Center – LUMC
      • Newcastle University
      • Profilomic
      • Universitätsklinikum Freiburg
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  • Publication highlights
    • Publication highlights
      • 229th ENMC international workshop: Limb girdle muscular dystrophies – nomenclature and reformed classification, 17-19 March 2017, Naarden, The Netherlands

        Volker Straub, Alexander Murphy, Bjarne Udd


        Tracking disease progression non‐invasively in Duchenne and Becker muscular dystrophies

        Pietro Spitali, Kristina Hettne, Roula Tsonaka, Mohammed Charrout, Janneke van den Bergen, Zaïda Koeks, Hermien E. Kan, Melissa T. Hooijmans, Andreas Roos, Volker Straub, Francesco Muntoni,
        Cristina Al‐Khalili‐Szigyarto, Marleen J.A. Koel‐Simmelink, Charlotte E. Teunissen, Hanns Lochmüller, Erik H. Niks, Annemieke Aartsma‐Rus


        Survival in patients with spinocerebellar ataxia types 1, 2, 3, and 6 (EUROSCA): a longitudinal cohort study

        Alhassane Diallo, Heike Jacobi, Arron Cook, Robyn Labrum, Prof Alexandra Durr, Prof Alexis Brice, Perrine Charles, Cecilia Marelli, Caterina Mariotti, Lorenzo Nanetti, Marta Panzeri, Maria Rakowicz, Anna Sobanska, Anna Sulek, Tanja Schmitz-Hübsch, Ludger Schöls, Holger Hengel, Prof Bela Melegh, Prof Alessandro Filla, Antonella Antenora, Jon Infante, Prof José Berciano, Bart P van de Warrenburg, Dagmar Timmann, Sylvia Boesch, Prof Massimo Pandolfo, Prof Jörg B Schulz, Peter Bauer, Paola Giunti, Jun-Suk Kang, Prof Thomas Klockgether, Sophie Tezenas du Montcel


        Recessive variants of MuSK are associated with late onset CMS and predominant limb girdle weakness

        David Owen, Ana Töpf, Veeramani Preethish‐Kumar, Paolo José Lorenzoni, Bas Vroling, Rosana Herminia Scola, Elza Dias‐Tosta, Argemiro Geraldo, Kiran Polavarapu, Saraswati Nashi, Daniel Cox, Teresinha Evangelista, John Dawson, Rachel Thompson, Jan Senderek, Steven Laurie, Sergi Beltran, Marta Gut, Ivo Gut, Atchayaram Nalini, Hanns Lochmüller


        RD-Connect, NeurOmics and EURenOmics: collaborative European initiative for rare diseases

        Hanns Lochmüller, Dorota M. Badowska, Rachel Thompson, Nine V. Knoers, Annemieke Aartsma-Rus, Ivo Gut, Libby Wood, Tina Harmuth, Andre Durudas, Holm Graessner, Franz Schaefer, Olaf Riess, RD-Connect consortium, NeurOmics consortium & EURenOmics consortium


        The Beta-Adrenergic Agonist Salbutamol Modulates Neuromuscular Junction Formation in Zebrafish Models of Human Myasthenic Syndromes

        Grace McMacken, Dan Cox, Andreas Roos, Juliane Müller, Roger Whittaker, Hanns Lochmüller


        Rare non-synonymous variants in SORT1 are associated with increased risk for frontotemporal dementia

        Stéphanie Philtjens, Sara Van Mossevelde, Julie van der Zee, Eline Wauters, Lubina Dillen, Mathieu Vandenbulcke, Rik Vandenberghe, Adrian Ivanoiu, Anne Sieben, Christiana Willems, Luisa Benussi, Roberta Ghidoni, Giuliano Binetti, Barbara Borroni, Alessandro Padovani, Pau Pastor, Monica Diez-Fairen, Miquel Aguilar, Alexandre de Mendonça, Gabriel Miltenberger-Miltényi, Isabel Hernández, Merce Boada, Agustín Ruiz, Benedetta Nacmiass, Sandro Sorbi, Maria Rosário Almeida, Isabel Santana, Jordi Clarimón, Alberto Lleó, Giovanni B. Frisoni, Raquel Sanchez-Valle, Albert Lladó, Estrella Gómez-Tortosa, Ellen Gelpi, Marleen Van den Broeck, Karin Peeters, Patrick Cras, Peter P. De Deyn, Sebastiaan Engelborghs, Marc Cruts, Christine Van


        PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease

        Manisha Juneja, Abdelkrim Azmi, Jonathan Baets, Andreas Roos, Matthew J Jennings, Paola Saveri, Chiara Pisciotta, Nathalie Bernard-Marissal, Bernard L Schneider, Catherine Verfaillie, Roman Chrast, Pavel Seeman, Angelika F Hahn, Peter de Jonghe, Stuart Maudsley, Rita Horvath, Davide Pareyson, Vincent Timmerman


        Cross-sectional serum metabolomic study of multiple forms of muscular dystrophy

        Pietro Spitali, Kristina Hettne, Roula Tsonaka, Ekrem Sabir, Alexandre Seyer, Jesse B.A. Hemerik, Jelle J. Goeman, Esther Picillo, Manuela Ergoli, Luisa Politano, Annemieke Aartsma-Rus


        Harmonising phenomics information for a better interoperability in the rare disease field

        Sylvie Maiellaa, Annie Olrya, Marc Hanauera, Valérie Lanneaua, Halima Lourghia, Bruno Donadillea, Charlotte Rodwella, Sebastian Köhlerc, Dominik Seelowc, Simon Juppe, Helen Parkinsone, Tudor Grozaf, Michael Brudnod, Peter N. Robinsonb, Ana Ratha


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Translocation of molecular chaperones to the titin springs is common in skeletal myopathy patients and affects sarcomere function

Authors

Andreas Unger, Lisa Beckendorf, Pierre Böhme, Rudolf Kley, Marion von Frieling-Salewsky, Hanns Lochmüller, Rolf Schröder, Dieter O. Fürst, Matthias Vorgerd and Wolfgang A. Linke

Journal

Acta Neuropathologica Communications, volume Neuroscience of Disease 2017, issue 5, pages 72

Publication date

September 2017

Abstract

Myopathies encompass a wide variety of acquired and hereditary disorders. The pathomechanisms include structural and functional changes affecting, e.g., myofiber metabolism and contractile properties. In this study, we observed increased passive tension (PT) of skinned myofibers from patients with myofibrillar myopathy (MFM) caused by FLNC mutations (MFM-filaminopathy) and limb-girdle muscular dystrophy type-2A due to CAPN3 mutations (LGMD2A), compared to healthy control myofibers. Because the giant protein titin determines myofiber PT, we measured its molecular size and the titin-to-myosin ratio, but found no differences between myopathies and controls. All-titin phosphorylation and site-specific phosphorylation in the PEVK region were reduced in myopathy, which would be predicted to lower PT. Electron microscopy revealed extensive ultrastructural changes in myofibers of various hereditary myopathies and also suggested massive binding of proteins to the sarcomeric I-band region, presumably heat shock proteins (HSPs), which can translocate to elastic titin under stress conditions. Correlative immunofluorescence and immunoelectron microscopy showed that two small HSPs (HSP27 and αB-crystallin) and the ATP-dependent chaperone HSP90 translocated to the titin springs in myopathy. The small HSPs, but not HSP90, were upregulated in myopathic versus control muscles. The titin-binding pattern of chaperones was regularly observed in Duchenne muscular dystrophy (DMD), LGMD2A, MFM-filaminopathy, MFM-myotilinopathy, titinopathy, and inclusion body myopathy due to mutations in valosin-containing protein, but not in acquired sporadic inclusion body myositis. The three HSPs also associated with elastic titin in mouse models of DMD and MFM-filaminopathy. Mechanical measurements on skinned human myofibers incubated with exogenous small HSPs suggested that the elevated PT seen in myopathy is caused, in part, by chaperone-binding to the titin springs. Whereas this interaction may be protective in that it prevents sarcomeric protein aggregation, it also has detrimental effects on sarcomere function. Thus, we identified a novel pathological phenomenon common to many hereditary muscle disorders, which involves sarcomeric alterations.

DOI link

10.1186/s40478-017-0474-0

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The NeurOmics project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 2012-305121.

 
   

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