A Heterozygous Mutation in the Filamin C Gene Causes an Unusual Nemaline Myopathy With Ring Fibers

J Neuropathol Exp Neurol. 2020 Aug 1;79(8):908-914. doi: 10.1093/jnen/nlaa052.


Autosomal dominant pathogenic variants in the filamin C gene (FLNC) have been associated with myofibrillar myopathies, distal myopathies, and isolated cardiomyopathies. Mutations in different functional domains of FLNC can cause various clinical phenotypes. A novel heterozygous missense variant c.608G>A, p.(Cys203Tyr) in the actin binding domain of FLCN was found to cause an upper limb distal myopathy (MIM #614065). The muscle MRI findings are similar to those observed in FLNC-myofibrillar myopathy (MIM #609524). However, the muscle biopsy revealed >20% of muscle fibers with nemaline bodies, in addition to numerous ring fibers and a predominance of type 1 fibers. Overall, this case shows some unique and rare aspects of FLNC-myopathy constituting a new morphologic phenotype of FLNC-related myopathies.

Keywords: Filamin C (FLNC); Filamin C-related myopathies; Muscle MRI; Nemaline bodies; Sarcomere disorganization.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Filamins / genetics
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Myopathies, Nemaline / genetics*
  • Myopathies, Nemaline / pathology*
  • Myopathies, Structural, Congenital / genetics*
  • Myopathies, Structural, Congenital / pathology*
  • Pedigree
  • Phenotype


  • Filamins