Recessive MYH7-related myopathy in two families

Sarah J. Beecroft, Martijn van de Locht, Josine M. de Winter, Coen A. Ottenheijm, Caroline A. Sewry, Shehla Mohammed, Monique M. Ryan, Ian R. Woodcock, Lauren Sanders, Rebecca Gooding, Mark R. Davis, Emily C. Oates, Nigel G. Laing, Gianina Ravenscroft, Catriona A. McLean, Heinz Jungbluth

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Myopathies due to recessive MYH7 mutations are exceedingly rare, reported in only two families to date. We describe three patients from two families (from Australia and the UK) with a myopathy caused by recessive mutations in MYH7. The Australian family was homozygous for a c.5134C > T, p.Arg1712Trp mutation, whilst the UK patient was compound heterozygous for a truncating (c.4699C > T; p.Gln1567*) and a missense variant (c.4664A > G; p.Glu1555Gly). All three patients shared key clinical features, including infancy/childhood onset, pronounced axial/proximal weakness, spinal rigidity, severe scoliosis, and normal cardiac function. There was progressive respiratory impairment necessitating non-invasive ventilation despite preserved ambulation, a combination of features often seen in SEPN1- or NEB-related myopathies. On biopsy, the Australian proband showed classical myosin storage myopathy features, while the UK patient showed multi-minicore like areas. To establish pathogenicity of the Arg1712Trp mutation, we expressed mutant MYH7 protein in COS-7 cells, observing abnormal mutant myosin aggregation compared to wild-type. We describe skinned myofiber studies of patient muscle and hypertrophy of type II myofibers, which may be a compensatory mechanism. In summary, we have expanded the phenotype of ultra-rare recessive MYH7 disease, and provide novel insights into associated changes in muscle physiology.

Original languageEnglish (US)
Pages (from-to)456-467
Number of pages12
JournalNeuromuscular Disorders
Issue number6
StatePublished - Jun 2019
Externally publishedYes


  • MYH7
  • Muscle physiology
  • Myosin storage myopathy
  • Myosinopathy
  • Next generation sequencing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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