Rare Manifestation of a c.290 C>T, p.Gly97Glu VCP Mutation

Creators: Jerath, Nivedita U.; Crockett, Cameron D.; Moore, Steven A.; Shy, Michael E.; Weihl, Conrad C.; Chou, Tsui-Fen; Grider, Tiffany; Gonzalez, Michael A.; Zuchner, Stephan; Swenson, Andrea

Abstract

Introduction. The valosin-containing protein (VCP) regulates several distinct cellular processes. Consistent with this, VCP mutations manifest variable clinical phenotypes among and within families and are a diagnostic challenge. Methods. A 60-year-old man who played ice hockey into his 50's was evaluated by electrodiagnostics, muscle biopsy, and molecular genetics.Results. With long-standing pes cavus and toe walking, our patient developed progressive weakness, cramps, memory loss, and paresthesias at age 52. An axonal sensorimotor neuropathy was found upon repeated testing at age 58. Neuropathic histopathology was present in the quadriceps, and exome sequencing revealed the VCP mutation c.290 C>T, p.Gly97Glu. Conclusions. Our patient reflects the clinical heterogeneity of VCP mutations, as his neurological localization is a spectrum between a lower motor neuron disorder and a hereditary axonal peripheral neuropathy such as CMT2. Our case demonstrates a rare manifestation of the c.290 C>T, pGly97Glu VCP mutation.

Additional Information

© 2015 Nivedita U. Jerath et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Received 27 January 2015; Accepted 12 March 2015. Michael E. Shy would like to acknowledge support from the National Institute of Neurological Disorders and Stroke (NINDS) and Office of Rare Diseases (U54, NS065712) as well as grants from the Muscular Dystrophy Association (MDA) and Charcot Marie Tooth Association (CMTA). Nivedita U. Jerath would like to acknowledge support from an MDA Clinical Research Training grant and a University of Iowa Internal Funding Initiatives award. Cameron D. Crockett received funding by NIH through the Iowa Wellstone Muscular Dystrophy Cooperative Research Center (U54, NS053672). Steven A. Moore is supported in part by NIH through the Iowa Wellstone Muscular Dystrophy Cooperative Research Center (U54, NS053672). Tsui-Fen Chou is supported by the National Center for Advancing Translational Sciences through UCLA CTSI Grant UL1TR000124 and the LA BioMed Seed Grant program (20826-01) and is a member of UCLA Johnson Comprehensive Cancer Center. Informed consent was obtained from the patient. The authors declare that there is no conflict of interests regarding the publication of this paper.

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