@article {567,
	title = {ACTN2 mutations cause "Multiple structured Core Disease" (MsCD).},
	journal = {Acta Neuropathol},
	volume = {137},
	year = {2019},
	month = {2019 03},
	pages = {501-519},
	abstract = {<p>The identification of genes implicated in myopathies is essential for diagnosis and for revealing novel therapeutic targets. Here we characterize a novel subclass of congenital myopathy at the morphological, molecular, and functional level. Through exome sequencing, we identified de novo ACTN2 mutations, a missense and a deletion, in two unrelated patients presenting with progressive early-onset muscle weakness and respiratory involvement. Morphological and ultrastructural analyses of muscle biopsies revealed a distinctive pattern with the presence of muscle fibers containing small structured cores and jagged Z-lines. Deeper analysis of the missense mutation revealed mutant alpha-actinin-2 properly localized to the Z-line in differentiating myotubes and its level was not altered in muscle biopsy. Modelling of the disease in zebrafish and mice by exogenous expression of mutated alpha-actinin-2 recapitulated the abnormal muscle function and structure seen in the patients. Motor deficits were noted in zebrafish, and muscle force was impaired in isolated muscles from AAV-transduced mice. In both models, sarcomeric disorganization was evident, while expression of wild-type alpha-actinin-2 did not result in muscle anomalies. The murine muscles injected with mutant ACTN2 displayed cores and Z-line defects. Dominant ACTN2 mutations were previously associated with cardiomyopathies, and our data demonstrate that specific mutations in the well-known Z-line regulator alpha-actinin-2 can cause a skeletal muscle disorder.</p>},
	issn = {1432-0533},
	doi = {10.1007/s00401-019-01963-8},
	author = {Lornage, Xavi{\`e}re and Romero, Norma B and Grosgogeat, Claire A and Malfatti, Edoardo and Donkervoort, Sandra and Marchetti, Michael M and Neuhaus, Sarah B and Foley, A Reghan and Labasse, Cl{\'e}mence and Schneider, Rapha{\"e}l and Carlier, Robert Y and Chao, Katherine R and Medne, Livija and Deleuze, Jean-Fran{\c c}ois and Orlikowski, David and B{\"o}nnemann, Carsten G and Gupta, Vandana A and Fardeau, Michel and B{\"o}hm, Johann and Laporte, Jocelyn}
}
