Nemaline Myopathy with Minicores Caused by Mutation of the CFL2 Gene Encoding the Skeletal Muscle Actin-Binding Protein, Cofilin-2

P.B. Agrawal, R.S. Greenleaf, K.K. Tomczak, V. Lehtokari, C. Wallgren-Pettersson, W. Wallefeld, Nigel Laing, B.T. Darras, S.K. Maciver, P.R. Dormitzer, A.H. Beggs

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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.
Original languageEnglish
Pages (from-to)162-167
JournalAmerican Journal of Human Genetics
Volume80
Issue number1
DOIs
Publication statusPublished - 2007

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    Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V., Wallgren-Pettersson, C., Wallefeld, W., Laing, N., Darras, B. T., Maciver, S. K., Dormitzer, P. R., & Beggs, A. H. (2007). Nemaline Myopathy with Minicores Caused by Mutation of the CFL2 Gene Encoding the Skeletal Muscle Actin-Binding Protein, Cofilin-2. American Journal of Human Genetics, 80(1), 162-167. https://doi.org/10.1086/510402