Novel mutations highlight the key role of the ankyrin repeat domain in TRPV4-mediated neuropathy.

ABSTRACT:

Objective

To characterize 2 novel TRPV4 mutations in 2 unrelated families exhibiting the Charcot-Marie-Tooth disease type 2C (CMT2C) phenotype.

Methods

Direct CMT gene testing was performed on 2 unrelated families with CMT2C. A 4-fold symmetric tetramer model of human TRPV4 was generated to map the locations of novel TRPV4 mutations in these families relative to previously identified disease-causing mutations (neuropathy, skeletal dysplasia, and osteoarthropathy). Effects of the mutations on TRPV4 expression, localization, and channel activity were determined by immunocytochemical, immunoblotting, Ca(2+) imaging, and cytotoxicity assays.

Results

Previous studies suggest that neuropathy-causing mutations occur primarily at arginine residues on the convex face of the TR

SUBMITTER: Sullivan JM 

PROVIDER: S-EPMC4811381 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature