A sporadic case of rippling muscle disease caused by a de novo caveolin-3 mutation.
OBJECTIVE
To determine the cause of sporadic rippling muscle disease (RMD) in a 24-year-old patient.


BACKGROUND
RMD is a rare myopathy characterized by percussion-induced rapid muscle contractions (PIRC), muscle mounding, and rippling waves. We have recently found that autosomal dominant RMD is caused by mutations in the caveolin-3 gene (CAV3) on chromosome 3p25. Possibly, increased activity of neuronal nitric oxide synthase (nNOS) contributes to the clinical characteristics of increased mechanical muscle hyperexcitability.


METHODS
Clinical examination, mutational analysis, and immunohistochemistry of muscle tissue were performed in a patient with sporadic RMD.


RESULTS
The authors observed a de novo CAV3 missense mutation Arg26Gln. Immunohistochemistry showed reduced caveolin-3 surface expression in a muscle biopsy. In addition, the authors found normal sarcolemmal nNOS expression and a reduced expression of alpha-dystroglycan in muscle fibers.


CONCLUSIONS
These data confirm that RMD is caused by CAV3 mutations. Moreover, there is evidence that CAV3 mutations may also be found in patients without a positive family history of RMD.
Vorgerd
M
M
Department of Neurology, Ruhr-University, Bochum, Germany. matthias.vorgerd@ruhr-uni-bochum.de
Ricker
K
K
Ziemssen
F
F
Kress
W
W
Goebel
H H
HH
Nix
W A
WA
Kubisch
C
C
Schoser
B G
BG
Mortier
W
W
D000328:Adult; D001706:Biopsy; D051244:Caveolin 3; D022461:Caveolins / Q000235:genetics*; D004576:Electromyography; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009132:Muscles / Q000473:pathology* / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*
D051244:Caveolin 3; D022461:Caveolins