2. Academic Validation
  3. A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease

A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease

  • Brain. 2014 Nov;137(Pt 11):2897-902. doi: 10.1093/brain/awu224.
Michael A Gonzalez 1,  Shawna M Feely 2,  Fiorella Speziani 1,  Alleene V Strickland 1,  Matt Danzi 1,  Chelsea Bacon 2,  Youjin Lee 3,  Tsui-Fen Chou 4,  Susan H Blanton 1,  Conrad C Weihl 3,  Stephan Zuchner 5,  Michael E Shy 6
Affiliations

Affiliations

  • 1 1 Dr John T Macdonald Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
  • 2 2 Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
  • 3 3 Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
  • 4 4 Division of Medical Genetics, Department of Paediatrics, Harbor-UCLA Medical Centre and Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA.
  • 5 1 Dr John T Macdonald Department of Human Genetics and John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL 33136, USA [email protected] [email protected].
  • 6 2 Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA [email protected] [email protected].
PMID: 25125609 DOI: 10.1093/brain/awu224
Abstract

Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia, hereditary spastic paraplegia, and 1-2% of familial amyotrophic lateral sclerosis. We identified a novel VCP mutation (p.Glu185Lys) segregating in an autosomal dominant Charcot-Marie-Tooth disease type 2 family. Functional studies showed that the Glu185Lys variant impaired autophagic function leading to the accumulation of immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2.

Keywords

autophagy; hereditary motor and sensory neuropathies; neurodegeneration; neuropathy; whole-exome sequencing.

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