Abstract
Myosin heavy chain (MyHC) is a major structural component of the striated muscle contractile apparatus. In adult human limb skeletal muscle, there are three major MyHC isoforms, slow/beta cardiac MyHC, MyHC IIa and MHC IIx, which are important for the functional characteristics of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression dependent on the mutated isoform, and also the type and location of the mutation. Myosin myopathy with external ophthalmoplegia is associated with mutations in MYH2, encoding for MyHC IIa that is mainly expressed in type 2A muscle fibers and is inherited in dominant as well as recessive manner. We present a family with myopathy with early onset proximal muscle weakness, facial muscle involvement and ophthalmoplegia. Muscle biopsy demonstrated lack of type 2A muscle fibers and genetic work up demonstrated that the disease was caused by a novel recessive MYH2 mutation: c.1009-1G>A resulting in skipping of exon 12, which is predicted to result in a frame shift and introducing at premature stop codon at position 347 (p.Ser337Leufs*11).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Oldfors A (2007) Hereditary myosin myopathies. Neuromuscul Disord 17:355–367
Tajsharghi H, Oldfors A (2013) Myosinopathies: pathology and mechanisms. Acta Neuropathol 125:3–18
Milone M, Wong LJ (2013) Diagnosis of mitochondrial myopathies. Mol Genet Metab 110:35–41
Darras BT, Friedman NR (2000) Metabolic myopathies: a clinical approach; part I. Pediatr Neurol 22:87–97
Martinsson T, Oldfors A, Darin N, Berg K, Tajsharghi H, Kyllerman M, Wahlström J (2000) Autosomal dominant myopathy: Missense mutation (Glu-706 to Lys) in the myosin heavy chain IIa gene. Proc Natl Acad Sci USA 97:14614–14619
D’Amico A, Fattori F, Bellacchio E, Catteruccia M, Servidei S, Bertini E (2013) A new de novo missense mutation in MYH2 expands clinical and genetic findings in hereditary myosin myopathies. Neuromuscul Disord 23:437–440
Cabrera-Serrano M, Fabian VA, Boutilier J, Wise C, Faiz F, Lamont PJ, Laing NG (2015) Adult onset distal and proximal myopathy with complete ophthalmoplegia associated with a novel de novo p.(Leu1877Pro) mutation in MYH2. Clin Genet 88:573–578
Darin N, Kyllerman M, Wahlstrom J, Martinsson T, Oldfors A (1998) Autosomal dominant myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles. Ann Neurol 44:242–248
Ochala J, Li M, Tajsharghi H, Kimber E, Tulinius M, Oldfors A, Larsson L (2007) Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction in single human muscle fibres. J Physiol 581:1283–1292
Tajsharghi H, Thornell LE, Darin N, Martinsson T, Kyllerman M, Wahlstrom J, Oldfors A (2002) Myosin heavy chain IIa gene mutation E706K is pathogenic and its expression increases with age. Neurology 58:780–786
Tajsharghi H, Hilton-Jones D, Raheem O, Saukkonen AM, Oldfors A, Udd B (2010) Human disease caused by loss of fast IIa myosin heavy chain due to recessive MYH2 mutations. Brain 133:1451–1459
Lossos A, Oldfors A, Fellig Y, Meiner V, Argov Z, Tajsharghi H (2013) MYH2 mutation in recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12. Brain 136:e238
Tajsharghi H, Hammans S, Lindberg C, Lossos A, Clarke NF, Mazanti I, Waddell LB, Fellig Y, Foulds N, Katifi H, Webster R, Raheem O, Udd B, Argov Z, Oldfors A (2014) Recessive myosin myopathy with external ophthalmoplegia associated with MYH2 mutations. Eur J Hum Genet 22:801–808
Kjellgren D, Stal P, Larsson L, Furst D, Pedrosa-Domellof F (2006) Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles. Invest Ophthalmol Vis Sci 47:4188–4193
Acknowledgments
This study was supported by the Swedish Research Council (project no. 07122, AO).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
The authors report no conflict of interest.
Ethical standards
This study has been performed in accordance with the ethical standards in the 1964 Declaration of Helsinki and its later amendments.
Rights and permissions
About this article
Cite this article
Willis, T., Hedberg-Oldfors, C., Alhaswani, Z. et al. A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness. J Neurol 263, 1427–1433 (2016). https://doi.org/10.1007/s00415-016-8154-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00415-016-8154-8