OMIM@xiajingbo:102565-4-FLNC JSONTXT

In affected members of an Italian family with autosomal dominant distal myopathy-4 (MPD4; 614065), Duff et al. (2011) identified a heterozygous 577G-A transition in exon 2 of the FLNC gene, resulting in an ala193-to-thr (A193T) substitution in a highly conserved residue in the CH2 domain in the actin-binding domain. The mutation was not found in 204 control chromosomes. The mutant protein had slightly decreased thermal stability and showed increased actin-binding activity compared to the wildtype protein. Nuclear localization was unaltered, but transfection resulted in the formation of intracellular protein aggregates. Duff et al. (2011) concluded that the disease mechanism somehow involves increased affinity for actin. The phenotype was characterized by adult onset of distal muscle weakness and atrophy affecting the upper and lower limbs, with nonspecific findings on muscle biopsy.

Annnotations VIEW JSON TextAE TextAE-Dev

  • Denotations: 14
  • Relations: 10
  • Modifications: 0