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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C
Nature Genetics, Volume 42, No. 2, Year 2010
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Description
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. © 2010 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Landouré, Guida
United Kingdom, London
University College London
United States, Bethesda
National Institute of Neurological Disorders and Stroke
Mali, Bamako
University of Bamako
Zdebik, Anselm A.
United Kingdom, London
University College London
Martinez, Tara L.
United States, Baltimore
Johns Hopkins University
United States, Baltimore
Johns Hopkins Bloomberg School of Public Health
Burnett, Barrington G.
United States, Bethesda
National Institute of Neurological Disorders and Stroke
Stanescu, Horia C.
United Kingdom, London
University College London
Inada, H.
United States, Cambridge
Harvard University
Shi, Yijun
United States, Bethesda
National Institute of Neurological Disorders and Stroke
Taye, Addis A.
United States, Bethesda
National Institute of Neurological Disorders and Stroke
Kong, Lingling
United States, Baltimore
Johns Hopkins University
Munns, Clare H.
United States, Baltimore
Johns Hopkins University
Choo, Shelly S.
United States, Cambridge
Harvard University
Phelps, Christopher B.
United States, Cambridge
Harvard University
Paudel, Reema
United Kingdom, London
Ucl Queen Square Institute of Neurology
Houlden, Henry H.
United Kingdom, London
Ucl Queen Square Institute of Neurology
Ludlow, Christy L.
United States, Harrisonburg
James Madison University
Caterina, Michael J.
United States, Baltimore
Johns Hopkins University
Gaudet, Rachelle
United States, Cambridge
Harvard University
Kleta, Robert
United Kingdom, London
University College London
Fischbeck, Kenneth H.
United States, Bethesda
National Institute of Neurological Disorders and Stroke
Sumner, Charlotte Jane
United States, Baltimore
Johns Hopkins University
Statistics
Citations: 290
Authors: 20
Affiliations: 8
Identifiers
Doi:
10.1038/ng.512
ISSN:
10614036
e-ISSN:
15461718
Research Areas
Genetics And Genomics