title: Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.
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.
authors.affiliation: Genomics Program, the Divisions of Genetics and Neonatology, Children's Hospital Boston, Boston, MA, 02115, USA.
authors.forename: Pankaj B
authors.initials: PB
authors.lastname: Agrawal
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Greenleaf
authors.forename: Kinga K
authors.initials: KK
authors.lastname: Tomczak
authors.forename: Vilma-Lotta
authors.initials: VL
authors.lastname: Lehtokari
authors.forename: Carina
authors.initials: C
authors.lastname: Wallgren-Pettersson
authors.forename: William
authors.initials: W
authors.lastname: Wallefeld
authors.forename: Nigel G
authors.initials: NG
authors.lastname: Laing
authors.forename: Basil T
authors.initials: BT
authors.lastname: Darras
authors.forename: Sutherland K
authors.initials: SK
authors.lastname: Maciver
authors.forename: Philip R
authors.initials: PR
authors.lastname: Dormitzer
authors.forename: Alan H
authors.initials: AH
authors.lastname: Beggs
mesh_terms: D000199:Actins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D051340:Cofilin 2 / Q000235:genetics* / Q000502:physiology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000502:physiology; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009210:Myofibrils / Q000378:metabolism / Q000473:pathology*; D017696:Myopathies, Nemaline / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010766:Phosphorylation
chemical_list: D000199:Actins; C495815:CFL2 protein, human; D051340:Cofilin 2; D008840:Microfilament Proteins