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
Genomics Program, the Divisions of Genetics and Neonatology, Children's Hospital Boston, Boston, MA, 02115, USA.
Am J Hum Genet. 2007 Jan;80(1):162-7. doi: 10.1086/510402. Epub 2006 Nov 14.
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.
杆状体肌病(NM)是一种先天性肌病,其特征为受影响的肌纤维出现肌无力和杆状体。已知有五个NM基因,均编码肌节细肌丝的组成成分。我们报告了第六个基因CFL2的鉴定,该基因编码肌动蛋白结合蛋白肌肉丝切蛋白-2,在两名患有先天性肌病的同胞中发生了突变。先证者的肌肉含有特征性的杆状体,以及偶尔出现的具有微小核心、同心层状体和F-肌动蛋白积聚区域的纤维。据报道,她患病的妹妹的肌肉表现出非特异性的肌病改变。先证者肌肉中的丝切蛋白-2水平显著降低,并且突变蛋白在大肠杆菌中表达时溶解性较差,这表明丝切蛋白-2的缺乏可能导致肌动蛋白丝的解聚减少,从而使其在杆状体、微小核心以及可能的同心层状体中积聚。