Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.
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.
Agrawal
Pankaj B
PB
Genomics Program, the Divisions of Genetics and Neonatology, Children's Hospital Boston, Boston, MA, 02115, USA.
Greenleaf
Rebecca S
RS
Tomczak
Kinga K
KK
Lehtokari
Vilma-Lotta
VL
Wallgren-Pettersson
Carina
C
Wallefeld
William
W
Laing
Nigel G
NG
Darras
Basil T
BT
Maciver
Sutherland K
SK
Dormitzer
Philip R
PR
Beggs
Alan H
AH
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
D000199:Actins; C495815:CFL2 protein, human; D051340:Cofilin 2; D008840:Microfilament Proteins