Abstract |
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.
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Authors | 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 |
Journal | Neuromuscular disorders : NMD
(Neuromuscul Disord)
Vol. 29
Issue 6
Pg. 456-467
(06 2019)
ISSN: 1873-2364 [Electronic] England |
PMID | 31130376
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2019 Elsevier B.V. All rights reserved. |
Chemical References |
- MYH7 protein, human
- Cardiac Myosins
- Myosin Heavy Chains
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Topics |
- Adolescent
- Adult
- Animals
- COS Cells
- Cardiac Myosins
(genetics, metabolism)
- Chlorocebus aethiops
- Family
- Female
- Humans
- Male
- Muscular Diseases
(diagnostic imaging, genetics, metabolism)
- Mutation
- Myofibrils
(metabolism, pathology)
- Myosin Heavy Chains
(genetics, metabolism)
- Phenotype
- Young Adult
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