Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Altered myogenesis and premature senescence underlie human TRIM32-related myopathy

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. and Paradas, C. (2019) Altered myogenesis and premature senescence underlie human TRIM32-related myopathy. Acta Neuropathologica Communications, 7 (1).

PDF - Published Version
Download (14MB) | Preview
Free to read:
*No subscription required


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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Comparative Genomics
Publisher: BioMed Central
Copyright: © 2019 The Author(s).
Item Control Page Item Control Page


Downloads per month over past year