| *601443 | ||||||||||||||||||
| COFILIN 2; CFL2 | ||||||||||||||||||
| Alternative titles; symbols | ||||||||||||||||||
| COFILIN, MUSCLE | ||||||||||||||||||
| HGNC Approved Gene Symbol: CFL2 | ||||||||||||||||||
| Cytogenetic location: 14q13.1 Genomic coordinates (GRCh37): 14:35,179,587 - 35,184,028 (from NCBI) | ||||||||||||||||||
| Gene Phenotype Relationships | ||||||||||||||||||
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| TEXT | ||||||||||||||||||
| Description | ||||||||||||||||||
| Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. (Gillett et al., 1996). Cofilin-2 is a member of the AC group of proteins that also includes cofilin-1 (CFL1) and destrin (DSTN; 609114), all of which regulate actin-filament dynamics (Bamburg et al., 1999; Maciver and Hussey, 2002). The CFL2 gene encodes a skeletal muscle-specific isoform (Vartiainen et al., 2002) localized to the thin filaments, where it exerts its effect on actin, in part through interactions with tropomyosins (Ono and Ono, 2002). | ||||||||||||||||||
| Mapping | ||||||||||||||||||
| Gillett et al. (1996) mapped CFL2, the human muscle-type (M-type) cofilin, to chromosome 14 by analysis of a somatic cell hybrid panel using an expressed sequence tag (EST) with homology to the mouse muscle-type cofilin and chicken cofilin. See also CFL1 (601442). | ||||||||||||||||||
| Molecular Genetics | ||||||||||||||||||
| Agrawal et al. (2007) used genomic PCR and DNA sequencing to screen the CFL2 gene in 113 unrelated patients with nemaline myopathy and 58 patients with clinical pathologic diagnoses of other congenital myopathies. None of the patients had known mutations in previously identified genes. In 2 sibs with nemaline myopathy (NEM7; 610687) in a large family of Middle Eastern origin, Agrawal et al. (2007) identified a homozygous mutation in the CFL2 gene (A35T; 601443.0001). The proband's muscle contained characteristic nemaline bodies, as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. 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. | ||||||||||||||||||
| ALLELIC VARIANTS (Selected Examples): | ||||||||||||||||||
| Table View | ||||||||||||||||||
| .0001 NEMALINE MYOPATHY 7 | ||||||||||||||||||
| CFL2, ALA35THR [dbSNP:rs80358250] | ||||||||||||||||||
| In 2 sisters in a family of Middle Eastern origin, Agrawal et al. (2007) found that nemaline myopathy with some unusual histopathologic and clinical features (NEM7; 610687) was related to homozygous mutation of the CFL2 gene, 103G-A, predicted to result in an alanine-to-threonine substitution at residue 35 (A35T). An unaffected sib, both unaffected parents, and a number of other members of the extended family were heterozygous for this change. Extensive intermarriage, with multiple consanguinity loops, strongly suggested identity by descent for the 2 mutant alleles, a supposition that was supported by linkage studies using flanking markers. The mutation was ruled out in 282 unaffected control individuals, including 91 originating from the same geographic region and ethnic group as the family. | ||||||||||||||||||
| REFERENCES | ||||||||||||||||||
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