Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

Myosin heavy chain IIa ge… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression increases with age.

Artikel i vetenskaplig tidskrift
Författare Homa Tajsharghi
Lars-Eric Thornell
Niklas Darin
Tommy Martinsson
Mårten Kyllerman
Jan Wahlström
Anders Oldfors
Publicerad i Neurology
Volym 58
Nummer/häfte 5
Sidor 780-6
ISSN 0028-3878
Publiceringsår 2002
Publicerad vid Institutionen för laboratoriemedicin , Avdelningen för patologi
Institutionen för kvinnors och barns hälsa, Avdelningen för pediatrik
Sidor 780-6
Språk en
Länkar www.ncbi.nlm.nih.gov/pubmed/1188924...
Ämnesord Adult, Aging, genetics, Alleles, Biopsy, Child, Gene Expression Regulation, Humans, Middle Aged, Muscle, Skeletal, metabolism, pathology, ultrastructure, Mutation, Missense, Myosin Heavy Chains, genetics, metabolism, Myositis, Inclusion Body, congenital, genetics, metabolism, pathology, Protein Isoforms, RNA, Messenger, genetics, metabolism, Vacuoles, ultrastructure
Ämneskategorier Cell- och molekylärbiologi

Sammanfattning

BACKGROUND: The authors recently described a new autosomal dominant myopathy (OMIM 605637 inclusion body myopathy 3) associated with a missense mutation in the myosin heavy chain (MyHC) IIa gene (MyHC IIa, Human Gene Map [HGM] locus MYH2). Young patients showed minor changes in their muscle biopsies, although dystrophic alterations and rimmed vacuoles with 15- to 20-nm tubulofilaments identical to those in sporadic inclusion body myositis (s-IBM) were observed in some of the adult (especially older) patients. The current study was undertaken to investigate the relation between expression of the mutant MyHC IIa and pathologic changes in muscle. METHODS: The expression of MyHC IIa in nine muscle specimens from six individuals carrying the mutation was analyzed by immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a new reverse transcriptase--PCR method to measure the relative abundance of the various MyHC transcripts. RESULTS: Young patients with muscle weakness and minor pathologic changes in muscle expressed MyHC IIa at undetectable levels. MyHC IIa was expressed at high levels in adults with a progressive clinical course and dystrophic muscle changes. In these cases, a large number of muscle fibers were hybrids with expression of more than one MyHC isoform. Both MyHC IIa alleles were equally expressed. The relative level of MyHC IIa transcripts exceeded that of the corresponding protein, indicating an increased turnover of mutated protein. MyHC IIa expression was a consistent finding in muscle fibers with rimmed vacuoles. CONCLUSIONS: The clear correlation between pathologic changes and expression of MyHC IIa indicates that defects in MyHC may lead not only to muscle weakness but also to muscle degeneration. The consistent expression of MyHC IIa in muscle fibers with rimmed vacuoles indicates that the breakdown of sarcomeric proteins is a key element in the pathogenesis of rimmed vacuoles of s-IBM type.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?