Journal article
Altered myogenesis and premature senescence underlie human TRIM32-related myopathy
Acta Neuropathologica Communications, Vol.7(1)
2019
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.
Details
- Title
- Altered myogenesis and premature senescence underlie human TRIM32-related myopathy
- Authors/Creators
- E. Servián-Morilla (Author/Creator) - Hospital Universitario Virgen del RocíoM. Cabrera-Serrano (Author/Creator) - Harry Perkins Institute of Medical ResearchE. Rivas-Infante (Author/Creator) - Harry Perkins Institute of Medical ResearchA. Carvajal (Author/Creator) - Hospital Universitario Virgen de las NievesP.J. Lamont (Author/Creator) - Harry Perkins Institute of Medical ResearchA.L. Pelayo-Negro (Author/Creator) - Marqués de Valdecilla University HospitalG. Ravenscroft (Author/Creator) - Harry Perkins Institute of Medical ResearchR. Junckerstorff (Author/Creator) - Royal Perth HospitalJ.M. Dyke (Author/Creator) - Royal Perth HospitalS. Fletcher (Author/Creator) - Murdoch UniversityA.M. Adams (Author/Creator) - Murdoch UniversityF. Mavillard (Author/Creator) - Hospital Universitario Virgen del RocíoM.A. Fernández-García (Author/Creator) - Neurology Department, Health in Code S.L., A Coruña, SpainJ.L. Nieto-González (Author/Creator) - Universidad de SevillaN.G. Laing (Author/Creator) - Harry Perkins Institute of Medical ResearchC. Paradas (Author/Creator) - Hospital Universitario Virgen del Rocío
- Publication Details
- Acta Neuropathologica Communications, Vol.7(1)
- Publisher
- BioMed Central
- Identifiers
- 991005540378807891
- Copyright
- © 2019 The Author(s).
- Murdoch Affiliation
- Centre for Comparative Genomics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.255 Musculoskeletal Disorders
- 1.255.628 Duchenne Muscular Dystrophy
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Biology & Biochemistry