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

doi:10.1093/brain/awu224

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

Research output: Contribution to journal › Article › peer-review

96 Scopus citations

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.

Original language	English
Pages (from-to)	2897-2902
Number of pages	6
Journal	Brain
Volume	137
Issue number	11
DOIs	https://doi.org/10.1093/brain/awu224
State	Published - Nov 2014

Keywords

Autophagy
Hereditary motor and sensory neuropathies
Neurodegeneration
Neuropathy
Whole-exome sequencing

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10.1093/brain/awu224

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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.",

keywords = "Autophagy, Hereditary motor and sensory neuropathies, Neurodegeneration, Neuropathy, Whole-exome sequencing",

author = "Gonzalez, {Michael A.} and Feely, {Shawna M.} and Fiorella Speziani and Strickland, {Alleene V.} and Matt Danzi and Chelsea Bacon and Youjin Lee and Chou, {Tsui Fen} and Blanton, {Susan H.} and Weihl, {Conrad C.} and Stephan Zuchner and Shy, {Michael E.}",

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AU - Gonzalez, Michael A.

AU - Feely, Shawna M.

AU - Speziani, Fiorella

AU - Strickland, Alleene V.

AU - Danzi, Matt

AU - Bacon, Chelsea

AU - Lee, Youjin

AU - Chou, Tsui Fen

AU - Blanton, Susan H.

AU - Weihl, Conrad C.

AU - Zuchner, Stephan

AU - Shy, Michael E.

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N2 - 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.

AB - 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.

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KW - Hereditary motor and sensory neuropathies

KW - Neurodegeneration

KW - Neuropathy

KW - Whole-exome sequencing

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

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Keywords

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