Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2019 May 8;20(1):78.
doi: 10.1186/s12881-019-0804-0.

A novel missense mutation in the MYH7 gene causes an uncharacteristic phenotype of myosin storage myopathy: a case report

Jean Mamelona  1 , Louisa Filice  2 , Youcef Oussedik  3 , Nicolas Crapoulet  4 , Rodney J Ouellette  4 , Alier Marrero  5   6
Affiliations
Case Reports

A novel missense mutation in the MYH7 gene causes an uncharacteristic phenotype of myosin storage myopathy: a case report

Jean Mamelona et al. BMC Med Genet. .

Abstract

Background: Few manuscripts have reported phenotypes of skeletal muscle myopathies caused by mutations in the head region of slow/cardiac beta-myosin heavy chain (MyHCI). Among the patients, some of them showed the phenotype of skeletal muscle weakness with the obvious clinical features of cardiomyopathy while others showed pure skeletal muscle weakness with no symptoms of cardiac involvement. Genotype-phenotype relationship regarding the effect of a mutation on MyHCI is complex. Questions regarding why some mutations cause cardiomyopathy or skeletal muscle disorders alone or a combination of both still need to be answered. More findings in genetic variation are needed to extend knowledge of mutations in the MYH7 gene linked to skeletal muscle disorders.

Case presentation: Here we present a female adult patient with a phenotype of childhood onset of muscular disorders and predominant involvement of thigh muscles with biopsy showing intrasarcoplasmic inclusion bodies. Whole exome sequencing showed that variant c.1370 T > G (p.Ile457Arg) in the MYH7 gene is a missense mutation possibly linked to the clinical findings. Our patient likely shows an uncharacteristic myosin storage myopathy associated with respiratory and cardiac involvement linked to a missense mutation in the head of MyHCI.

Conclusions: Given this mutation is located within the motor domain of MyHCI, this might affect the regulation of myosin mechano-chemical activity during the contractile cycle. Consequently, this potentially damaging effect can be easily amplified within the network of ~ 300-myosin molecules forming the thick filament and therefore become cumulatively deleterious, affecting, in turn, the overall organization and performance of sarcomere.

Keywords: Case report; MYH7; Missense mutation; Myosin storage myopathy; Slow/cardiac beta-myosin heavy chain.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the Research Ethics Board of Vitalité Health Network, of the province of New Brunswick, Canada. Written informed consents for the use of medical information and genetic analysis were obtained from the patient.

Consent for publication

Written consent was obtained from the patient for the publication of medical information.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Relevant history of the patient organized into a timeline
Fig. 2
Fig. 2
Results of muscle biopsy of left quadriceps. a H&E stain showing end-stage muscle. Scattered clusters of viable muscle fibres show marked variation in fiber size and numerous internal nuclei. b H&E stain showing scattered fibers with abundant intrasarcoplasmic vacuoles. c Negative control for p62 stain. d Transverse view of fibres displaying dark coloured intrasarcoplasmic inclusion bodies on p62 stain (Black arrow). Original magnifications: A: 10×, B: 10×, C: 40×, D: 40×
Fig. 3
Fig. 3
Partial electropherograms of the genomic region covering the MYH7 gene, with the representation showing the coding strand. Top. Control subject; Bottom. Patient, carrying variant NM_000257.3: c.1370 T > G (p.Ile457Arg) in a heterozygous status. The location of mutated nucleotide is highlighted in grey
See this image and copyright information in PMC

References

    1. Krendel M, Mooseker MS. Myosins: tails (and heads) of functional diversity. Physiology. 2005;20:239–251. doi: 10.1152/physiol.00014.2005. - DOI - PubMed
    1. Tajsharghi H, Oldfors A. Myosinopathies: pathology and mechanisms. Acta Neuropathol. 2013;125:3–18. doi: 10.1007/s00401-012-1024-2. - DOI - PMC - PubMed
    1. Colegrave M, Peckham M. Structural implications of β-cardiac myosin heavy chain mutations in human disease. Anat Rec. 2014;297:1670–1680. doi: 10.1002/ar.22973. - DOI - PubMed
    1. Buvoli M, Hamady M, Leinwand LA, Knight R. Bioinformatics assessment of β-myosin mutations reveals myosin high sensitivity to mutations. Trends Cardiovasc Med. 2008;18(4):141–149. doi: 10.1016/j.tcm.2008.04.001. - DOI - PMC - PubMed
    1. Darin N, Tajsharghi H, Ostman-Smith I, Gilljam T, Oldfors A. New skeletal myopathy and cardiomyopathy associated with a missense mutation in MYH7. Neurology. 2007;68(23):2041–2042. doi: 10.1212/01.wnl.0000264430.55233.72. - DOI - PubMed

Publication types