Embryonic myosin mutations T187I and R672C result in mechanical and structural dysfunction in hiPSC derived skeletal myotubes

Abstract

Distal arthrogryposis (DA) is a skeletal muscle disorder characterized by joint contractures at various parts of the body, predominantly in the distal extremities. DA is associated with syndromes like Freeman-Sheldon (FSS), caused by mutations in the sarcomeric protein-encoding gene MYH3 responsible for generating embryonic skeletal muscle myosin during development. We previously reported (Racca et al., 2015) that demembranated myofibrils from affected individuals expressing the R672C mutation in MYH3 exhibited lower specific force and prolonged relaxation.