Related Experiment Videos
Myopathies associated with myosin heavy chain mutations
A Oldfors1, H Tajsharghi, N Darin
1Department of Pathology, Sahlgrenska University Hospital, Göteborg, Sweden. anders.oldfors@pathology.gu.se
Summary
Mutations in myosin heavy chain (MyHC) cause congenital myopathies. These "myosin myopathies" involve muscle weakness and, in some cases, progressive pathology, highlighting MyHC
Area of Science:
- Molecular biology and genetics of muscle function.
- Biochemistry of muscle contraction and myosin motor activity.
Background:
- Myosin heavy chain (MyHC) is a molecular motor essential for muscle contraction, comprising a head domain with ATPase activity and a rod region.
- Three main MyHC isoforms (Type I/MYH7, IIa/MYH2, IIx/MYH1) are expressed in human skeletal muscle.
- While MYH7 mutations cause cardiomyopathy, skeletal myopathies linked to MyHC mutations were previously rare.
Purpose of the Study:
- To investigate the association of specific MyHC mutations with congenital myopathies.
- To characterize the clinical and pathological features of these novel myosin myopathies.
- To explore the impact of exercise on disease progression in affected patients.
Main Methods:
- Genetic analysis to identify mutations in MyHC genes.
- Histopathological examination of muscle biopsies to assess fiber pathology and protein deposition.
- Clinical evaluation of patients, including assessment of muscle strength and disease progression.
- Monitoring the effects of endurance training on myosin isoform expression.
Main Results:
- A heterozygous Glu706Lys mutation in MyHC IIa (MYH2) is linked to a familial congenital myopathy with variable phenotypes.
- Some adult patients with MyHC IIa mutations exhibit progressive myopathy with rimmed vacuoles and inclusion body myositis-like filaments.
- Endurance training altered myosin isoform expression (fast to slow shift) but did not reduce MyHC IIa levels.
- A heterozygous Arg1845Trp mutation in MyHC I (MYH7) causes 'Myosin storage myopathy' with subsarcolemmal MyHC I deposits and slowly progressive weakness.
Conclusions:
- Mutations in MyHC genes (MYH2 and MYH7) are identified as causes of distinct congenital myopathies, termed 'myosin myopathies'.
- These findings expand the spectrum of muscle diseases associated with myosin dysfunction.
- The study establishes a novel class of genetic muscle disorders linked to MyHC gene mutations.