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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. [ABSTRACT FROM AUTHOR]

Molecular and Cellular Biology

The article focuses on a study conducted by researcher Matthias Heidenreich and colleagues on tuning of mechanoreceptors by mutations inactivating the potassium channel KCNQ4. In the study, KCNQ4 is found in the peripheral nerve endings of hair follicle from mice and humans and explains touch sensitivity in mice and humans and describes gene mutation which establishes KCNQ4 as a molecular marker and modulates touch sensitivity in humans and mice.