ArticleHuman molecular genetics2015
The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Unsafe Care and Fake News in Freeman-Burian Syndrome.Clinical case reports · 2025Article
- Functional assessment of a novel biallelic MYH3 variation causing CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B).Molecular genetics & genomic medicine · 2024Article
- Homologous mutations in human β, embryonic, and perinatal muscle myosins have divergent effects on molecular power generation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Measuring the Contractile Kinetics of Isolated Myofibrils from Human-Induced Pluripotent Stem Cell Derived Cardiomyocyte (hiPSC-CM) Models of Cardiomyopathy.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Variants inHGG advances · 2023Article
- Variants inmedRxiv : the preprint server for health sciences · 2023Article
- Diagnostic work-up and phenotypic characteristics of a family with variable severity of distal arthrogryposis type 2B (Sheldon-Hall syndrome) and TNNT3 pathogenic variant.Frontiers in genetics · 2022Article
- Article
- Review
- Prolonged myosin binding increases muscle stiffness in Drosophila models of Freeman-Sheldon syndrome.Biophysical journal · 2021Article
- MYH3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin.EMBO molecular medicine · 2020Article
- Myosin dynamics during relaxation in mouse soleus muscle and modulation by 2'-deoxy-ATP.The Journal of physiology · 2020Article
- Identification and Recent Approaches for Evaluation and Management of Rehabilitation Concerns for Patients with Freeman-Burian Syndrome: Principles for Global Treatment.Journal of pediatric genetics · 2020Review
- Drosophila myosin mutants model the disparate severity of type 1 and type 2B distal arthrogryposis and indicate an enhanced actin affinity mechanism.Skeletal muscle · 2020Article
- Defective sarcomere organization and reduced larval locomotion and fish survival in slow muscle heavy chain 1 (smyhc1) mutants.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Host genetics influence the rumen microbiota and heritable rumen microbial features associate with feed efficiency in cattle.Microbiome · 2019Article
- Myosin heavy chain mutations that cause Freeman-Sheldon syndrome lead to muscle structural and functional defects in Drosophila.Developmental biology · 2019Article
- Freeman-Burian syndrome.Orphanet journal of rare diseases · 2019Review
- Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman-Sheldon syndrome.Molecular biology of the cell · 2019Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Distal arthrogryposis is the most common known heritable cause of congenital contractures (e.g. clubfoot) and results from mutations in genes that encode proteins of the contractile complex of skeletal muscle cells. Mutations are most frequently found in MYH3 and are predicted to impair the function of embryonic myosin. We measured the contractile properties of individual skeletal muscle cells and the activation and relaxation kinetics of isolated myofibrils from two adult individuals with an R672C substitution in embryonic myosin and distal arthrogryposis syndrome 2A (DA2A) or Freeman-Sheldon syndrome. In R672C-containing muscle cells, we observed reduced specific force, a prolonged time to relaxation and incomplete relaxation (elevated residual force). In R672C-containing muscle myofibrils, the initial, slower phase of relaxation had a longer duration and slower rate, and time to complete relaxation was greatly prolonged. These observations can be collectively explained by a small subpopulation of myosin cross-bridges with greatly reduced detachment kinetics, resulting in a slower and less complete deactivation of thin filaments at the end of contractions. These findings have important implications for selecting and testing directed therapeutic options for persons with DA2A and perhaps congenital contractures in general.
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