his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Human disease caused by loss of fast IIa myosin heavy chain due to recessive MYH2 mutations
Department of Pathology, Institute of Biomedicine, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden.ORCID iD: 0000-0001-8854-5213
Department of Neurology, West Wing, John Racliffe Hospital, Oxford, UK.
Neuromuscular Centre, Tampere University and Hospital, Tampere, Finland.
Department of Neurology, Central Hospital of Northern Karelia, Joensuu, Finland.
Show others and affiliations
2010 (English)In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 133, no 5, 1451-1459 p.Article in journal (Refereed) Published
Abstract [en]

Striated muscle myosin heavy chain is a molecular motor protein that converts chemical energy into mechanical force. It is a major determinant of the physiological properties of each of the three muscle fibre types that make up the skeletal muscles. Heterozygous dominant missense mutations in myosin heavy chain genes cause various types of cardiomyopathy and skeletal myopathy, but the effects of myosin heavy chain null mutations in humans have not previously been reported. We have identified the first patients lacking fast type 2A muscle fibres, caused by total absence of fast myosin heavy chain IIa protein due to truncating mutations of the corresponding gene MYH2. Five adult patients, two males and three females, from three unrelated families in UK and Finland were clinically assessed and muscle biopsy was performed in one patient from each family. MYH2 was sequenced and the expression of the corresponding transcripts and protein was analysed in muscle tissue. The patients had early-onset symptoms characterized by mild generalized muscle weakness, extraocular muscle involvement and relatively favourable prognosis. Muscle biopsy revealed myopathic changes including variability of fibre size, internalized nuclei, and increased interstitial connective and adipose tissue. No muscle fibres expressing type IIa myosin heavy chain were identified and the MYH2 transcripts were markedly reduced. All patients were compound heterozygous for truncating mutations in MYH2. The parents were unaffected, consistent with recessive mutations. Our findings show that null mutations in the fast myosin heavy chain IIa gene cause early onset myopathy and demonstrate that this isoform is necessary for normal muscle development and function. The relatively mild phenotype is interesting in relation to the more severe phenotypes generally seen in relation to recessive null mutations in sarcomeric proteins.

Place, publisher, year, edition, pages
Oxford University Press, 2010. Vol. 133, no 5, 1451-1459 p.
National Category
Neurology
Research subject
Medical sciences
Identifiers
URN: urn:nbn:se:his:diva-11958DOI: 10.1093/brain/awq083ISI: 000277225700023PubMedID: 20418530Scopus ID: 2-s2.0-77951921511OAI: oai:DiVA.org:his-11958DiVA: diva2:906951
Available from: 2016-02-25 Created: 2016-02-25 Last updated: 2016-03-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Tajsharghi, Homa
In the same journal
Brain
Neurology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 514 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf