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Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome.
Nat Genet. 2006 May; 38(5):561-5.NGen

Abstract

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

Authors+Show Affiliations

Department of Human Genetics, University of Utah, Salt Lake City, Utah, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16642020

Citation

Toydemir, Reha M., et al. "Mutations in Embryonic Myosin Heavy Chain (MYH3) Cause Freeman-Sheldon Syndrome and Sheldon-Hall Syndrome." Nature Genetics, vol. 38, no. 5, 2006, pp. 561-5.
Toydemir RM, Rutherford A, Whitby FG, et al. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nat Genet. 2006;38(5):561-5.
Toydemir, R. M., Rutherford, A., Whitby, F. G., Jorde, L. B., Carey, J. C., & Bamshad, M. J. (2006). Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nature Genetics, 38(5), 561-5.
Toydemir RM, et al. Mutations in Embryonic Myosin Heavy Chain (MYH3) Cause Freeman-Sheldon Syndrome and Sheldon-Hall Syndrome. Nat Genet. 2006;38(5):561-5. PubMed PMID: 16642020.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. AU - Toydemir,Reha M, AU - Rutherford,Ann, AU - Whitby,Frank G, AU - Jorde,Lynn B, AU - Carey,John C, AU - Bamshad,Michael J, Y1 - 2006/04/16/ PY - 2005/12/20/received PY - 2006/03/08/accepted PY - 2006/4/28/pubmed PY - 2006/8/2/medline PY - 2006/4/28/entrez SP - 561 EP - 5 JF - Nature genetics JO - Nat Genet VL - 38 IS - 5 N2 - 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 of the most severe multiple congenital contracture (that is, arthrogryposis) syndromes, and nearly one-third of all cases of Sheldon-Hall syndrome (SHS), the most common distal arthrogryposis. FSS and SHS mutations affect different myosin residues, demonstrating that MYH3 genotype is predictive of phenotype. A structure-function analysis shows that nearly all of the MYH3 mutations are predicted to interfere with myosin's catalytic activity. These results add to the growing body of evidence showing that congenital contractures are a shared outcome of prenatal defects in myofiber force production. Elucidation of the genetic basis of these syndromes redefines congenital contractures as unique defects of the sarcomere and provides insights about what has heretofore been a poorly understood group of disorders. SN - 1061-4036 UR - https://www.unboundmedicine.com/medline/citation/16642020/Mutations_in_embryonic_myosin_heavy_chain__MYH3__cause_Freeman_Sheldon_syndrome_and_Sheldon_Hall_syndrome_ L2 - https://doi.org/10.1038/ng1775 DB - PRIME DP - Unbound Medicine ER -