#610687
NEMALINE MYOPATHY 7; NEM7

Phenotype Gene Relationships
Location Phenotype Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
14q13.1 Nemaline myopathy 7 610687 CFL2 601443

TEXT
A number sign (#) is used with this entry because this form of nemaline myopathy is caused by mutation in the gene encoding cofilin-2 (CFL2; 601443).

For a discussion of genetic heterogeneity of nemaline myopathy, see 161800.

Clinical Features
Agrawal et al. (2007) described 2 sibs from a large consanguineous Middle Eastern family, identified in a screen of patients with congenital myopathies, with nemaline myopathy. Both patients had similar clinical presentations, with hypotonia noted at birth, delayed early motor milestones, frequent falls, and inability to run. The elder sister at age 16 years could walk short distances but used a wheelchair outside the house. Muscle biopsy showed nonspecific myopathic changes. The younger sib at age 9 years was ambulant. Muscle biopsy showed characteristic nemaline bodies as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. The course of the disease in both sibs was like that of typical nemaline myopathy, but the distribution of weakness was distinct, without significant facial weakness or foot drop.

Molecular Genetics
On the basis of the role of cofilin-2 in regulation of sarcomeric actin filaments, Agrawal et al. (2007) screened 113 unrelated patients with nemaline myopathy and 58 patients with clinicopathologic diagnoses of other congenital myopathies for mutations in the CFL2 gene. They found a homozygous missense mutation (601443.0001) in 2 sibs from a large consanguineous Middle Eastern family with nemaline myopathy. Agrawal et al. (2007) estimated that the frequency of CFL2 mutations in patients with nemaline myopathy is well below 0.6%.

REFERENCES
1. Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V.-L., Wallgren-Pettersson, C., Wallefeld, W., Laing, N. G., Darras, B. T., Maciver, S. K., Dormitzer, P. R., Beggs, A. H. Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2. Am. J. Hum. Genet. 80: 162-167, 2007. [PubMed: 17160903, related citations] [Full Text: Elsevier Science, Pubget]

Creation Date: Victor A. McKusick : 1/5/2007
Edit History: alopez : 01/05/2007