The pathogenesis of <i>ACTA1</i>‐related congenital fiber type disproportion

Clarke, Nigel F.; Ilkovski, Biljana; Cooper, Sandra T.; Valova, Valentina A.; Robinson, Phillip J.; Nonaka, Ikuya; Feng, Juanjuan; Marston, Steven B.; North, Klaus

doi:10.1002/ana.21112

Cited by 68 publications

(46 citation statements)

References 25 publications

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“…For the CFTD mutants, our biochemical data compliment the results reported by Clarke et al [Clarke et al, 2007]. These authors showed, using immunoprecipitation, that mutants a-actin L221P, D292V, P332S incorporate in filaments and that a-actin D292V and a-actin P332S function in an in vitro motility assay [Clarke et al, 2007]. This is consistent with our observation that the mutants are folded to a functional conformation, given they interact with the ABPs tested.…”

Section: Discussion Cftd and Ccd Causing A-actin Mutants Are Correctlsupporting

confidence: 94%

“…Using our in vitro folding and band-shift assay, we showed that all five mutants fold correctly, are stable and bind to the ABPs DNAseI and VDBP. For the CFTD mutants, our biochemical data compliment the results reported by Clarke et al [Clarke et al, 2007]. These authors showed, using immunoprecipitation, that mutants a-actin L221P, D292V, P332S incorporate in filaments and that a-actin D292V and a-actin P332S function in an in vitro motility assay [Clarke et al, 2007].…”

Section: Discussion Cftd and Ccd Causing A-actin Mutants Are Correctlsupporting

confidence: 93%

“…This is consistent with our observation that the mutants are folded to a functional conformation, given they interact with the ABPs tested. However for a-actin D292V the interaction with tropomyosin seems to be particularly disrupted [Clarke et al, 2007].…”

Section: Discussion Cftd and Ccd Causing A-actin Mutants Are Correctlmentioning

confidence: 99%

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α‐Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures

Vandamme¹,

Rommelaere²,

Lambert³

et al. 2009

Cell Motil. Cytoskeleton

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Central core disease (CCD), congenital fibre type disproportion (CFTD), and nemaline myopathy (NM) are earlyonset clinically heterogeneous congenital myopathies, characterized by generalized muscle weakness and hypotonia. All three diseases are associated with alpha-skeletal muscle actin mutations. We biochemically characterized the CCD and CFTD causing actin mutants and show that all mutants fold correctly and are stable. Expression studies in fibroblasts, myoblasts, and myotubes show that these mutants incorporate in filamentous structures. However they do not intercalate between the nascent z-lines in differentiating muscle cell cultures. We also show that the distribution of mitochondria and of the ryanodine receptors, and calcium release properties from ryanodine receptors, are unchanged in myotubes expressing the CCD causing mutants. CFTD causing mutants induce partly similar phenotypes as NM associated ones, such as rods and thickened actin fibers in cell culture. Our results suggest that molecular mechanisms behind CFTD and NM may be partly related.

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Section: Discussion Cftd and Ccd Causing A-actin Mutants Are Correctlsupporting

confidence: 94%

Section: Discussion Cftd and Ccd Causing A-actin Mutants Are Correctlsupporting

confidence: 93%

See 1 more Smart Citation

α‐Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures

Vandamme¹,

Rommelaere²,

Lambert³

et al. 2009

Cell Motil. Cytoskeleton

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“…There is marked genetic and clinico-pathological overlap with other congenital myopathies, in particular NM and RYR1-related myopathies, and although in many patients the histopathological appearance of "pure" CFTD persists, in others additional histopathological features such as nemaline rods, central nuclei or cores may evolve over time [15,[122][123][124][125][126][127]. CFTD is most commonly due to mutations in TPM3 and RYR1 and less frequently due to mutations in ACTA1 and SEPN1.…”

Section: Congenital Fibre Type Disproportionmentioning

confidence: 99%

Current and future therapeutic approaches to the congenital myopathies

Jungbluth

Ochala

Treves

et al. 2017

Seminars in Cell & Developmental Biology

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a b s t r a c tThe congenital myopathies -including Central Core Disease (CCD), Multi-minicore Disease (MmD), Centronuclear Myopathy (CNM), Nemaline Myopathy (NM) and Congenital Fibre Type Disproportion (CFTD) -are a genetically heterogeneous group of early-onset neuromuscular conditions characterized by distinct histopathological features, and associated with a substantial individual and societal disease burden. Appropriate supportive management has substantially improved patient morbidity and mortality but there is currently no cure. Recent years have seen an exponential increase in the genetic and molecular understanding of these conditions, leading to the identification of underlying defects in proteins involved in calcium homeostasis and excitation-contraction coupling, thick/thin filament assembly and function, redox regulation, membrane trafficking and/or autophagic pathways. Based on these findings, specific therapies are currently being developed, or are already approaching the clinical trial stage. Despite undeniable progress, therapy development faces considerable challenges, considering the rarity and diversity of specific conditions, and the size and complexity of some of the genes and proteins involved.The present review will summarize the key genetic, histopathological and clinical features of specific congenital myopathies, and outline therapies already available or currently being developed in the context of known pathogenic mechanisms. The relevance of newly discovered molecular mechanisms and novel gene editing strategies for future therapy development will be discussed. © 2016 Elsevier Ltd. All rights reserved.

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“…MYH1 and MYH2 subtype mainly express in the fast muscle fibers (Smerdu et al, 1994), which determine the explosive power and speed. ACTA1 gene-encoding actins, which attach to the skeletal muscle actin filaments, play a very important role in the process of muscle contraction (Clarke et al, 2007). Genes involved in hypoxia response and thermal response were also detected rich in the yak muscle tissue that may play very important roles in adapting to deprived oxygen, low pressure and arctic alpine plateau environment.…”

Section: Discussionmentioning

confidence: 99%

Profiling of the yak skeletal muscle tissue gene expression and comparison with the domestic cattle by genome array

Wang

Liu

Zhang

2014

Animal

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Of all the mammals of the world, the yak lives at the highest altitude area of more than 3000 m. Comparison between yak and cattle of the low-altitude areas will be informative in studying animal adaptation to higher altitudes. To investigate the molecular mechanism involved in meat quality differences between the two Chinese special varieties Qinghai yak and Qinchuan cattle, 12 chemical-physical characteristics of the longissimus dorsi muscle related to meat quality were compared at the age of 36 months, and the gene expression profiles were constructed by utilizing the bovine genome array. Significant analysis of microarrays was used to identify the differentially expressed genes. Gene ontology and pathway analysis were performed by a free Web-based Molecular Annotation System 2.0. The results reveal~11 000 probes representing about 10 000 genes that were detected in both the Qinghai yak and Qinchuan cattle. A total of 1922 genes were shown to be differentially expressed, 633 probes were upregulated and 1259 probes were downregulated in the muscle tissue of Qinghai yak that were mainly involved in ubiquitin-mediated proteolysis, muscle growth regulation, glucose metabolism, immune response and so on. Quantitative real-time PCR (qRT-PCR) was performed to validate some differentially expressed genes identified by microarray. Further analysis implied that animals living at a high altitude may supply energy by more active protein catabolism and glycolysis compared with those living in the plain areas. Our results establish the groundwork for further studies on yaks' meat quality and will be beneficial in improving the yaks' breeding by molecular biotechnology.

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The pathogenesis of ACTA1‐related congenital fiber type disproportion

Cited by 68 publications

References 25 publications

α‐Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures

α‐Skeletal muscle actin mutants causing different congenital myopathies induce similar cytoskeletal defects in cell line cultures

Current and future therapeutic approaches to the congenital myopathies

Profiling of the yak skeletal muscle tissue gene expression and comparison with the domestic cattle by genome array

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