A novel VCP mutation underlies scapuloperoneal muscular dystrophy and dropped head syndrome featuring lobulated fibers.
BACKGROUND
Valosin-containing protein (VCP) is a ubiquitously expressed, multifunctional AAA-ATPase protein. Its dominant mutations cause hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) or amyotrophic lateral sclerosis. The pattern of muscle weakness in IBMPFD patients is variable and includes limb-girdle, scapuloperoneal, distal, or axial distributions.


METHODS
We report a 63-year-old man with progressive scapuloperoneal weakness, head drop, and hyperCKemia since age 40 years. Electromyography showed myopathic changes and rare myotonic discharges. Muscle biopsy revealed numerous lobulated fibers, few fibers with glycogen accumulation, and rare fibers with polyglucosan bodies. Rimmed vacuoles and congophilic inclusions, often seen in IBMPFD, were absent. VCP sequencing identified a novel heterozygous c. 1160G>A mutation resulting in p.Asn387Ser substitution.


CONCLUSIONS
Our patient broadens the pathological spectrum of VCP-myopathy and emphasizes the importance of VCP analysis in patients with scapuloperoneal muscular dystrophy despite the absence of Paget disease, dementia, rimmed vacuoles, or intracellular amyloid deposition.
Department of Neurology, University of Colorado School of Medicine, Anschutz Medical Campus, 12631 East 17th Avenue, Aurora, Colorado, USA.
Teerin
T
Liewluck
Margherita
M
Milone
Michelle L
ML
Mauermann
Melissa
M
Castro-Couch
Jane H
JH
Cerhan
Naveen S
NS
Murthy
D000251:Adenosine Triphosphatases / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D006801:Humans; D007738:Kyphosis / Q000150:complications / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000074405:Valosin Containing Protein
D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
VCP; dropped head syndrome; glycogen; lobulated fiber; polyglucosan body; scapuloperoneal muscular dystrophy; valosin-containing protein