title: Severe neuropathy with leaky connexin32 hemichannels.
abstract: X-linked Charcot-Marie-Tooth disease is one of a set of diseases caused by mutations in gap junction proteins called connexins. We identified a connexin32 missense mutation (F235C) in a girl with unusually severe neuropathy. The localization and trafficking of the mutant protein in cell culture was normal, but electrophysiological studies showed that the mutation caused abnormal hemichannel opening, with excessive permeability of the plasma membrane and decreased cell survival. Abnormal leakiness of connexin hemichannels is likely a mechanism of cellular toxicity in this and perhaps other diseases caused by connexin mutations.
authors.affiliation: Department of Neurology, Parkinson's Disease and Movement Disorders Center, University of Pennsylvania Medical Center, Philadelphia, PA 19107, USA. liangg@pahosp.com
authors.forename: Grace S Lin
authors.initials: GS
authors.lastname: Liang
authors.forename: Marta
authors.initials: M
authors.lastname: de Miguel
authors.forename: Juan M
authors.initials: JM
authors.lastname: Gómez-Hernández
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Glass
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
authors.forename: Mark
authors.initials: M
authors.lastname: Mintz
authors.forename: Luis C
authors.initials: LC
authors.lastname: Barrio
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Fischbeck
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015139:Blotting, Southern; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D017630:Connexins / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D015640:Ion Channel Gating; D009865:Oocytes / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000502:physiology; D014981:Xenopus; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein