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

Michael A. Gonzalez, Shawna M. Feely, Fiorella Speziani, Alleene V. Strickland, Matt Danzi, Chelsea Bacon, Youjin Lee, Tsui-Fen Chou, Susan H. Blanton, Conrad C. Weihl, Stephan Zuchner, Michael E. Shy
2014 Brain  
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
more » ... immature autophagosomes. VCP mutations should thus be considered for genetically undefined Charcot-Marie-Tooth disease type 2.
doi:10.1093/brain/awu224 pmid:25125609 pmcid:PMC4208462 fatcat:fb7oedncdzfybghawxe4s2jjgy