title: A novel mutation in VCP causes Charcot-Marie-Tooth Type 2 disease.
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.
authors.affiliation: 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.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Gonzalez
authors.affiliation: 2 Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
authors.forename: Shawna M
authors.initials: SM
authors.lastname: Feely
authors.affiliation: 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.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Speziani
authors.affiliation: 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.
authors.forename: Alleene V
authors.initials: AV
authors.lastname: Strickland
authors.affiliation: 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.
authors.forename: Matt
authors.initials: M
authors.lastname: Danzi
authors.affiliation: 2 Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Bacon
authors.affiliation: 3 Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: Youjin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: 4 Division of Medical Genetics, Department of Paediatrics, Harbor-UCLA Medical Centre and Los Angeles Biomedical Research Institute, Torrance, CA 90502, USA.
authors.forename: Tsui-Fen
authors.initials: TF
authors.lastname: Chou
authors.affiliation: 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.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Blanton
authors.affiliation: 3 Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: Conrad C
authors.initials: CC
authors.lastname: Weihl
authors.affiliation: 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 michael-shy@uiowa.edu szuchner@med.miami.edu.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zuchner
authors.affiliation: 2 Department of Neurology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA michael-shy@uiowa.edu szuchner@med.miami.edu.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Shy
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000235:genetics*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein
keywords: autophagy; hereditary motor and sensory neuropathies; neurodegeneration; neuropathy; whole-exome sequencing