A novel VCP mutation underlies scapuloperoneal muscular dystrophy and dropped head syndrome featuring lobulated fibers

ABSTRACT Introduction: 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 pa...

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Published in:Muscle & nerve 2014-08, Vol.50 (2), p.295-299
Main Authors: Liewluck, Teerin, Milone, Margherita, Mauermann, Michelle L., Castro‐Couch, Melissa, Cerhan, Jane H., Murthy, Naveen S.
Format: Article
Language:English
Subjects:
Adenosine Triphosphatases - genetics
Cell Cycle Proteins - genetics
dropped head syndrome
glycogen
Humans
Kyphosis - complications
Kyphosis - genetics
lobulated fiber
Male
Middle Aged
Muscular dystrophy
Muscular Dystrophy, Emery-Dreifuss - complications
Muscular Dystrophy, Emery-Dreifuss - genetics
Mutation
Mutation - genetics
polyglucosan body
scapuloperoneal muscular dystrophy
Valosin Containing Protein
VCP
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Summary:ABSTRACT Introduction: 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. Case Report: 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. Muscle Nerve 50:295–299, 2014
ISSN:0148-639X
1097-4598
DOI:10.1002/mus.24290