uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Embryonic myosin heavy-chain mutations cause distal arthrogryposis and developmental myosin myopathy that persists postnatally
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
Show others and affiliations
2008 (English)In: Archives of Neurology, ISSN 0003-9942, E-ISSN 1538-3687, Vol. 65, no 8, 1083-1090 p.Article in journal (Refereed) Published
Abstract [en]

Background: Myosin is a molecular motor and the essential part of the thick filament of striated muscle. The expression of myosin heavy-chain (MyHC) isoforms is developmentally regulated. The embryonic isoform encoded from MYH3 (OMIM *160720) is expressed during fetal life. Recently, mutations in MYH3 were demonstrated to be associated with congenital joint contractures, that is, Freeman-Sheldon and Sheldon-Hall syndromes, which are both distal arthrogryposis syndromes. Mutations in other MyHC isoforms cause myopathy. It is unknown whether MYH3 mutations cause myopathy because muscle tissue has not been studied. Objectives: To determine whether novel MYH3 mutations are associated with distal arthrogryposis and to demonstrate myopathic changes in muscle biopsy specimens from 4 patients with distal arthrogryposis and MYH3 mutations. Design: In a cohort of patients with distal arthrogryposis, we analyzed the entire coding sequence of MYH3. Muscle biopsy specimens were obtained, and in addition to morphologic analysis, the expression of MyHC isoforms was investigated at the protein and transcript levels. Results: We identified patients from 3 families with novel MYH3 mutations. These mutations affect developmentally conserved residues that are located in different regions of the adenosine triphosphate-binding pocket of the MyHC head. The embryonic (MYH3) isoform was not detected in any of the muscle biopsy samples, indicating a normal developmental downregulation of MYH3 in these patients. However, morphologic analysis of muscle biopsy specimens from the 4 patients revealed mild and variable myopathic features and a pathologic upregulation of the fetal MyHC isoform (MYH8) in 1 patient. Conclusions: Distal arthrogryposis associated with MYH3 mutations is secondary to myosin myopathy, and postnatal muscle manifestations are variable.

Place, publisher, year, edition, pages
2008. Vol. 65, no 8, 1083-1090 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-152139ISI: 000258377100009OAI: oai:DiVA.org:uu-152139DiVA: diva2:412528
Available from: 2011-04-25 Created: 2011-04-25 Last updated: 2011-04-25Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Women's and Children's Health
In the same journal
Archives of Neurology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 177 hits
ReferencesLink to record
Permanent link

Direct link