| http://purl.uniprot.org/citations/30701273 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30701273 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30701273 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00401-019-01963-8"xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.org/dc/terms/identifier | "doi:10.1007/s00401-019-01963-8"xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Schneider R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Schneider R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Deleuze J.F."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Deleuze J.F."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Boehm J."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Boehm J."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Boennemann C.G."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Boennemann C.G."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Carlier R.Y."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Carlier R.Y."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Chao K.R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Chao K.R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Donkervoort S."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Donkervoort S."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Fardeau M."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Fardeau M."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Foley A.R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Foley A.R."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Grosgogeat C.A."xsd:string |
| http://purl.uniprot.org/citations/30701273 | http://purl.uniprot.org/core/author | "Grosgogeat C.A."xsd:string |