Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome.

摘要: The genetic basis of most conditions characterized by congenital contractures is largely unknown. Here we show that mutations in the embryonic myosin heavy chain (MYH3) gene cause Freeman-Sheldon syndrome (FSS), one severe multiple contracture (that is, arthrogryposis) syndromes, and nearly one-third all cases Sheldon-Hall (SHS), common distal arthrogryposis. FSS SHS affect different residues, demonstrating MYH3 genotype predictive phenotype. A structure-function analysis shows are predicted to interfere with myosin's catalytic activity. These results add growing body evidence showing a shared outcome prenatal defects myofiber force production. Elucidation these syndromes redefines as unique sarcomere provides insights about what has heretofore been poorly understood group disorders.