title: Congenital myopathy caused by a novel missense mutation in the CFL2 gene.
abstract: Nemaline myopathy and myofibrillar myopathy are heterogeneous myopathies that both comprise early-onset forms. We present two sisters from a consanguineous Iraqi Kurdish family with predominant axial and limb girdle weakness. Muscle biopsies showed features of both nemaline myopathy and myofibrillar myopathy. We performed homozygosity mapping in both siblings using an Affymetrix 250K Nspl SNP array. One of the overlapping homozygous regions harbored the gene CFL2. Because a mutation in CFL2 was identified in a family with nemaline myopathy, we performed sequence analysis of the gene and a novel homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met) of CFL2 was identified in both siblings. CFL2 encodes the protein cofilin-2, which plays an important role in regulation of sarcomeric actin filaments. To our knowledge, this is the second family in which a mutation in CFL2 causes an autosomal recessive form of congenital myopathy with features of both nemaline and myofibrillar myopathy. Given the clinical variability and the multitude of histological features of congenital myopathies, CFL2 sequence analysis should be considered in patients presenting with an autosomal recessive form of congenital myopathy.
authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. c.ockeloen@antrg.umcn.nl
authors.forename: C W
authors.initials: CW
authors.lastname: Ockeloen
authors.forename: H J
authors.initials: HJ
authors.lastname: Gilhuis
authors.forename: R
authors.initials: R
authors.lastname: Pfundt
authors.forename: E J
authors.initials: EJ
authors.lastname: Kamsteeg
authors.forename: P B
authors.initials: PB
authors.lastname: Agrawal
authors.forename: A H
authors.initials: AH
authors.lastname: Beggs
authors.forename: A
authors.initials: A
authors.lastname: Dara Hama-Amin
authors.forename: A
authors.initials: A
authors.lastname: Diekstra
authors.forename: N V A M
authors.initials: NV
authors.lastname: Knoers
authors.forename: M
authors.initials: M
authors.lastname: Lammens
authors.forename: N
authors.initials: N
authors.lastname: van Alfen
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D002648:Child; D051340:Cofilin 2 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D046529:Microscopy, Electron, Transmission; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D009136:Muscular Dystrophies / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense / Q000235:genetics*; D055815:Young Adult
chemical_list: C495815:CFL2 protein, human; D051340:Cofilin 2; D009124:Muscle Proteins; D000251:Adenosine Triphosphatases