Scalco, RS;
Gardiner, AR;
Pitceathly, RDS;
Hilton-Jones, D;
Schapira, AH;
Turner, C;
Parton, M;
... Quinlivan, R; + view all
(2016)
CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: expanding the phenotypic spectrum of caveolinopathies.
Neuromuscular Disorders
, 26
(8)
pp. 504-510.
10.1016/j.nmd.2016.05.006.
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Abstract
Rhabdomyolysis is often due to a combination of environmental trigger(s) and genetic predisposition; however, the underlying genetic cause remains elusive in many cases. Mutations in CAV3 lead to various neuromuscular phenotypes with partial overlap, including limb girdle muscular dystrophy type 1C (LGMD1C), rippling muscle disease, distal myopathy and isolated hyperCKemia. Here we present a series of eight patients from seven families presenting with exercise intolerance and rhabdomyolysis caused by mutations in CAV3 diagnosed by next generation sequencing (NGS) (n=6). Symptoms included myalgia (n=7), exercise intolerance (n=6) and episodes of rhabdomyolysis (n=2). Percussion-induced rapid muscle contractions (PIRCs) were seen in five out of six patients examined. A previously reported heterozygous mutation in CAV3 (p.T78M) and three novel variants (p.V14I, p.F41S, p.F54V) were identified. Caveolin-3 immunolabeling in muscle was normal in 3/4 patients however, immunoblotting showed more than 50% reduction of caveolin-3 in five patients compared with controls. This case series demonstrates that exercise intolerance, myalgia and rhabdomyolysis may be caused by CAV3 mutations and broadens the phenotypic spectrum of caveolinopathies. In our series immunoblotting was a more sensitive method to detect reduced caveolin-3 levels than immunohistochemistry in skeletal muscle. Patients presenting with muscle pain, exercise intolerance and rhabdomyolysis should be routinely tested for PIRCs as this may be an important clinical clue for caveolinopathies, even in the absence of other “typical” features. The use of NGS may expand current knowledge concerning inherited diseases, and unexpected/atypical phenotypes may be attributed to well-known human disease genes.
| Type: | Article |
|---|---|
| Title: | CAV3 mutations causing exercise intolerance, myalgia and rhabdomyolysis: expanding the phenotypic spectrum of caveolinopathies |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.nmd.2016.05.006 |
| Publisher version: | http://dx.doi.org/10.1016/j.nmd.2016.05.006 |
| Language: | English |
| Additional information: | Copyright © 2016 Elsevier B.V. All rights reserved. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher. |
| Keywords: | CAV3; Rhabdomyolysis; Myoglobinuria; Caveolinopathy; Exercise Intolerance; Myalgia |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1496854 |
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