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Pathogenic Variants...
Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
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Donkervoort, S. (author)
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Kutzner, C. E. (author)
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Hu, Y. (author)
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Lornage, X. (author)
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Rendu, J. (author)
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Stojkovic, T. (author)
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Baets, J. (author)
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Neuhaus, S. B. (author)
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Tanboon, J. (author)
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Maroofian, R. (author)
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Bolduc, V. (author)
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Mroczek, M. (author)
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Conijn, S. (author)
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Kuntz, N. L. (author)
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Topf, A. (author)
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Monges, S. (author)
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Lubieniecki, F. (author)
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McCarty, R. M. (author)
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Chao, K. R. (author)
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Governali, S. (author)
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Bohm, J. (author)
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Boonyapisit, K. (author)
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Malfatti, E. (author)
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Sangruchi, T. (author)
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Horkayne-Szakaly, I. (author)
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- Oldfors Hedberg, Carola, 1969 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Efthymiou, S. (author)
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Noguchi, S. (author)
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Djeddi, S. (author)
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Iida, A. (author)
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di Rosa, G. (author)
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Fiorillo, C. (author)
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Salpietro, V. (author)
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- Darin, Niklas, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics
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Faure, J. (author)
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Houlden, H. (author)
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- Oldfors, Anders, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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Nishino, I. (author)
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de Ridder, W. (author)
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Straub, V. (author)
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Pokrzywa, W. (author)
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Laporte, J. (author)
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Foley, A. R. (author)
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Romero, N. B. (author)
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Ottenheijm, C. (author)
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Hoppe, T. (author)
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Bonnemann, C. G. (author)
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 107:6, s. 1078-1095
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http://www.cell.com/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
Subject headings
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- The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Keyword
- Genetics & Heredity
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Donkervoort, S.
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Kutzner, C. E.
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Hu, Y.
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Lornage, X.
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Rendu, J.
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Stojkovic, T.
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show more...
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Baets, J.
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Neuhaus, S. B.
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Tanboon, J.
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Maroofian, R.
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Bolduc, V.
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Mroczek, M.
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Conijn, S.
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Kuntz, N. L.
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Topf, A.
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Monges, S.
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Lubieniecki, F.
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McCarty, R. M.
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Chao, K. R.
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Governali, S.
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Bohm, J.
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Boonyapisit, K.
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Malfatti, E.
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Sangruchi, T.
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Horkayne-Szakaly ...
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Oldfors Hedberg, ...
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Efthymiou, S.
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Noguchi, S.
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Djeddi, S.
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Iida, A.
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di Rosa, G.
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Fiorillo, C.
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Salpietro, V.
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Darin, Niklas, 1 ...
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Faure, J.
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Houlden, H.
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Oldfors, Anders, ...
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Nishino, I.
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de Ridder, W.
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Straub, V.
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Pokrzywa, W.
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Laporte, J.
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Foley, A. R.
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Romero, N. B.
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Ottenheijm, C.
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Hoppe, T.
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Bonnemann, C. G.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
- Articles in the publication
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American Journal ...
- By the university
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University of Gothenburg