Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3168
Title: Altered myogenesis and premature senescence underlie human TRIM32-related myopathy
Authors: Servián-Morilla, E.
Cabrera-Serrano, M.
Rivas-Infante, E.
Carvajal, A.
Lamont, P. J.
Pelayo-Negro, A. L.
Ravenscroft, G.
Junckerstorff, R.
Dyke, J. M.
Fletcher, S.
Adams, A. M.
Mavillard, F.
Fernández-García, M. A.
Nieto-González, J. L.
Laing, N. G.
Paradas, C.
metadata.dc.contributor.authoraffiliation: [Servian-Morilla,E; Cabrera-Serrano,M; Mavillard,F; Paradas,C] Neuromuscular Disorders Unit, Department of Neurology, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. [Servian-Morilla,E; Cabrera-Serrano,M; Mavillard,F; Nieto-González,JL; Paradas,C] Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. [Cabrera-Serrano,M; Rivas-Infante,E; Lamont,PJ; Ravenscroft,G; Laing,NG] Centre for Medical Research, University of Western Australia, Harry Perkins Institute of Medical Research, Perth, Australia. [Rivas-Infante,E] Department of Neuropathology, Hospital U. Virgen del Rocío/ Instituto de Biomedicina de Sevilla (IBiS), Sevilla, Spain. [Carvajal,A] Neuromuscular Unit, Hospital Virgen de las Nieves, Granada, Spain. [Pelayo-Negro,AL] Neurology Department, University Hospital Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain. [Junckerstorff,R; Dyke,JM] PathWest Laboratory Medicine WA, Section of Neuropathology, Royal Perth Hospital, Perth, WA, Australia. [Fletcher,S; Adams,AM] Centre for Comparative Genomics, Murdoch University, Perth, Australia. [Fletcher,S; Adams,AM] Perron Institute for Neurological and Translational Science, University of Western Australia, Nedlands, Australia. [Fernández-García,MA] Neurology Department, Health in Code S.L., A Coruña, Spain. [Nieto-González,JL] Department of Medical Physiology and Biophysics, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Keywords: Muscle dystrophy;TRIM32;E3 ubiquitin-ligase;Proliferation/differentiation;Autophagy;Muscular dystrophies;Distrofias musculares;Cell proliferation;Proliferación celular;Cell differentiation;Diferenciación celular;Autofagia
metadata.dc.subject.mesh: Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Musculoskeletal Development::Muscle Development
Medical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular Diseases
Medical Subject Headings::Anatomy::Cells::Stem Cells::Myoblasts
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Pedigree
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Ligases::Ubiquitin-Protein Ligase Complexes::Ubiquitin-Protein Ligases
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation
Medical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular Diseases::Muscular Disorders, Atrophic::Muscular Dystrophies
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Autophagy
Issue Date: 1-Mar-2019
Publisher: BioMed Central Ltd.
Citation: Servián-Morilla E, Cabrera-Serrano M, Rivas-Infante E, Carvajal A, Lamont PJ, Pelayo-Negro AL, et al. Altered myogenesis and premature senescence underlie human TRIM32-related myopathy. Acta Neuropathol Commun. 2019 Mar 1;7(1):30.
Abstract: TRIM32 is a E3 ubiquitin -ligase containing RING, B-box, coiled-coil and six C-terminal NHL domains. Mutations involving NHL and coiled-coil domains result in a pure myopathy (LGMD2H/STM) while the only described mutation in the B-box domain is associated with a multisystemic disorder without myopathy (Bardet-Biedl syndrome type11), suggesting that these domains are involved in distinct processes. Knock-out (T32KO) and knock-in mice carrying the c.1465G > A (p.D489N) involving the NHL domain (T32KI) show alterations in muscle regrowth after atrophy and satellite cells senescence. Here, we present phenotypical description and functional characterization of mutations in the RING, coiled-coil and NHL domains of TRIM32 causing a muscle dystrophy. Reduced levels of TRIM32 protein was observed in all patient muscle studied, regardless of the type of mutation (missense, single amino acid deletion, and frameshift) or the mutated domain. The affected patients presented with variable phenotypes but predominantly proximal weakness. Two patients had symptoms of both muscular dystrophy and Bardet-Biedl syndrome. The muscle magnetic resonance imaging (MRI) pattern is highly variable among patients and families. Primary myoblast culture from these patients demonstrated common findings consistent with reduced proliferation and differentiation, diminished satellite cell pool, accelerated senescence of muscle, and signs of autophagy activation.
URI: http://hdl.handle.net/10668/3168
metadata.dc.relation.publisherversion: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-019-0683-9
metadata.dc.identifier.doi: 10.1186/s40478-019-0683-9
ISSN: 2051-5960 (Online)
Appears in Collections:01- Artículos - Hospital Virgen de las Nieves
01- Artículos - Hospital Virgen del Rocío
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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