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Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2 |
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| Authors: | Agrawal Pankaj B Greenleaf Rebecca S Tomczak Kinga K Lehtokari Vilma-Lotta Wallgren-Pettersson Carina Wallefeld William Laing Nigel G Darras Basil T Maciver Sutherland K Dormitzer Philip R Beggs Alan H |
| Affiliation: | a Genomics Program (P.B.A.; R.S.G.; K.K.T.; A.H.B.) b Division of Genetics (P.B.A.; R.S.G.; K.K.T.; A.H.B.) c Division of Neonatology (P.B.A.) d Division of Laboratory of Molecular Medicine (P.R.D.) e Department of Medicine, and Department of Neurology (B.T.D.) f Children’s Hospital Boston, and Harvard Medical School (P.B.A.; K.K.T.; B.T.D.; P.R.D.; A.H.B.) g Boston; The Folkhälsan Institute of Genetics and the Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, Helsinki (V.-L.L.; C.W.-P.) h Molecular Neurogenetics Laboratory, Centre for Medical Research, West Australian Institute for Medical Research, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Australia (W.W.; N.G.L.) i Centre for Integrative Physiology, College of Medicine, University of Edinburgh, Edinburgh, United Kingdom (S.K.M.) |
| Abstract: | Nemaline myopathy (NM) is a congenital myopathy characterized by muscle weakness and nemaline bodies in affected myofibers. Five NM genes, all encoding components of the sarcomeric thin filament, are known. We report identification of a sixth gene, CFL2, encoding the actin-binding protein muscle cofilin-2, which is mutated in two siblings with congenital myopathy. The proband’s muscle contained characteristic nemaline bodies, as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. Her affected sister’s muscle was reported to exhibit nonspecific myopathic changes. Cofilin-2 levels were significantly lower in the proband’s muscle, and the mutant protein was less soluble when expressed in Escherichia coli, suggesting that deficiency of cofilin-2 may result in reduced depolymerization of actin filaments, causing their accumulation in nemaline bodies, minicores, and, possibly, concentric laminated bodies. |
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