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

作者:Gonzalez Michael A; Feely Shawna M; Speziani Fiorella; Strickland Alleene V; Danzi Matt; Bacon Chelsea; Lee Youjin; Chou Tsui Fen; Blanton Susan H; Weihl Conrad C; Zuchner Stephan; Shy Michael E*
来源:Brain, 2014, 137(11): 2897-2902.
DOI:10.1093/brain/awu224

摘要

Mutations in VCP have been reported to account for a spectrum of phenotypes that include inclusion body myopathy with Paget%26apos;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.

  • 出版日期2014-11