Abstract
Myosin myopathies comprise a group of inherited diseases caused by mutations in myosin heavy chain (MyHC) genes. Homozygous or compound heterozygous truncating MYH2 mutations have been demonstrated to cause recessive myopathy with ophthalmoplegia, mild-to-moderate muscle weakness and complete lack of type 2A muscle fibers. In this study, we describe for the first time the clinical and morphological characteristics of recessive myosin IIa myopathy associated with MYH2 missense mutations. Seven patients of five different families with a myopathy characterized by ophthalmoplegia and mild-to-moderate muscle weakness were investigated. Muscle biopsy was performed to study morphological changes and MyHC isoform expression. Five of the patients were homozygous for MYH2 missense mutations, one patient was compound heterozygous for a missense and a nonsense mutation and one patient was homozygous for a frame-shift MYH2 mutation. Muscle biopsy demonstrated small or absent type 2A muscle fibers and reduced or absent expression of the corresponding MyHC IIa transcript and protein. We conclude that mild muscle weakness and ophthalmoplegia in combination with muscle biopsy demonstrating small or absent type 2A muscle fibers are the hallmark of recessive myopathy associated with MYH2 mutations.
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Acknowledgements
The study was supported by grants from the Swedish Research Council (AO and HT), Agnes Ginges Fund for Human Neurogenetics (AL and ZA) and the Australian National Health and Medical Research Council grants 1022707, 1031893 and 1035828 (NFC).
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Tajsharghi, H., Hammans, S., Lindberg, C. et al. Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations. Eur J Hum Genet 22, 801–808 (2014). https://doi.org/10.1038/ejhg.2013.250
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DOI: https://doi.org/10.1038/ejhg.2013.250
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