UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C

Landoure, G; Zdebik, AA; Martinez, TL; Burnett, BG; Stanescu, HC; Inada, H; Shi, YJ; ... Sumner, CJ; + view all (2010) Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. NAT GENET , 42 (2) 170 - U109. 10.1038/ng.512. Gold open access

Abstract

Charcot-Marie-Tooth disease type 2C (CMT2C) is an autosomal dominant neuropathy characterized by limb, diaphragm and laryngeal muscle weakness. Two unrelated families with CMT2C showed significant linkage to chromosome 12q24.11. We sequenced all genes in this region and identified two heterozygous missense mutations in the TRPV4 gene, C805T and G806A, resulting in the amino acid substitutions R269C and R269H. TRPV4 is a well-known member of the TRP superfamily of cation channels. In TRPV4-transfected cells, the CMT2C mutations caused marked cellular toxicity and increased constitutive and activated channel currents. Mutations in TRPV4 were previously associated with skeletal dysplasias. Our findings indicate that TRPV4 mutations can also cause a degenerative disorder of the peripheral nerves. The CMT2C-associated mutations lie in a distinct region of the TRPV4 ankyrin repeats, suggesting that this phenotypic variability may be due to differential effects on regulatory protein-protein interactions.

Type: Article
Title: Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C
Open access status: An open access publication
DOI: 10.1038/ng.512
Publisher version: http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC28126...
Keywords: CATION CHANNEL TRPV4, ANKYRIN REPEAT DOMAIN, SENSORY NEUROPATHY, HEREDITARY MOTOR, ION-CHANNEL, ACTIVATION, MODEL, MICE, EXPRESSION, BIND
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Nephrology
URI: http://discovery.ucl.ac.uk/id/eprint/163072
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item