dc.creator | Servián Morilla, Emilia | es |
dc.creator | Cabrera Serrano, Macarena | es |
dc.creator | Carvajal, A. | es |
dc.creator | Lamont, P.J. | es |
dc.creator | Pelayo Negro, A. L. | es |
dc.creator | Ravenscroft, G. | es |
dc.creator | Junckerstorff, R. | es |
dc.creator | Dyke, J.M | es |
dc.creator | Fletcher, S. | es |
dc.creator | Adams, A. M. | es |
dc.creator | Fernández García, M. A. | es |
dc.creator | Nieto González, José Luis | es |
dc.creator | Laing, N. G. | es |
dc.creator | Rivas, Eloy | es |
dc.creator | Mavillard Saborido, Fabiola | es |
dc.creator | Paradas, Carmen | es |
dc.date.accessioned | 2019-05-24T11:13:46Z | |
dc.date.available | 2019-05-24T11:13:46Z | |
dc.date.issued | 2019-03-01 | |
dc.identifier.issn | 2051-5960 | es |
dc.identifier.uri | https://hdl.handle.net/11441/86807 | |
dc.description.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 knockin
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. | es |
dc.description.sponsorship | Health Institute Carlos III PI16-01843 JR15/00042 | es |
dc.description.sponsorship | FEDER PI16-01843 JR15/00042 | es |
dc.description.sponsorship | Fundación Progreso y Salud, Junta de Andalucía PI-0085-2016 | es |
dc.description.sponsorship | Australian National Health and Medical Research Council (NHMRC) APP1122952 APP1117510 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Springer Nature | es |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Muscle dystrophy | es |
dc.subject | TRIM32 | es |
dc.subject | E3 ubiquitin -ligase | es |
dc.subject | Proliferation/differentiation | es |
dc.subject | Autophagy | es |
dc.title | Altered myogenesis and premature senescence underlie human TRIM32-related myopathy | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | es |
dc.relation.projectID | PI16-01843 | es |
dc.relation.projectID | JR15/00042 | es |
dc.relation.projectID | PI-0085-2016 | es |
dc.relation.projectID | APP1122952 | es |
dc.relation.projectID | APP1117510 | es |
dc.relation.publisherversion | https://doi.org/10.1186/s40478-019-0683-9 | es |
dc.identifier.doi | 10.1186/s40478-019-0683-9 | es |
idus.format.extent | 16 p. | es |
dc.journaltitle | Acta Neuropathologica Communications | es |
dc.publication.volumen | 7 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 30-1 | es |
dc.publication.endPage | 30-16 | es |