Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV4

Title: TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: a report of three patients.

Authors: Tae-Joon Cho, Kazu Matsumoto, Virginia Fano, Jin Dai, Ok-Hwa Kim, Jong Hee Chae, Won Joon Yoo, Yuji Tanaka, Yoshito Matsui, Iori Takigami, Soledad Monges, Bernhard Zabel, Katsuji Shimizu, Gen Nishimura, Ekkehart Lausch, Shiro Ikegawa

Journal, date & volume: Am. J. Med. Genet. A, 2012 Apr , 158A, 795-802

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22419508

Abstract
Heterozygous missense mutations of transient receptor potential vanilloid 4 channel (TRPV4) cause a spectrum of skeletal disorders, including brachyolmia, spondylometaphyseal dysplasia Kozlowski type, metatropic dysplasia, parastremmatic dysplasia, and spondyloepimetaphyseal dysplasia Maroteaux type. Similarly, heterozygous missense mutations of TRPV4 cause a spectrum of peripheral neuropathy, including hereditary motor and sensory neuropathy type IIC, congenital spinal muscular atrophy, and scapuloperoneal spinal muscular atrophy. There are no apparent differences in the amino acid positions affected or type of change predicted by the TRPV4 mutations responsible for the two disease spectrums; nevertheless, no fundamental phenotypic overlap has been shown between the two spectrums. Here, we report on three patients who had both skeletal dysplasia and peripheral neuropathy caused by heterozygous TRPV4 missense mutations. The skeletal and neurologic phenotypes of these patients covered the wide spectrum of reported TRPV4-pathies (disease caused by TRPV4 mutations). The molecular data are complementary, proving that "neuropathic" mutations can cause skeletal dysplasia but also the "skeletopathic" mutations can lead to neuropathies. Our findings suggest that pathogenic mechanisms of TRPV4-pathies in skeletal and nervous systems are not always mutually exclusive and provide further evidence that there is no clear genotype-phenotype correlation for either spectrum. Co-occurrence of skeletal dysplasia and degenerative neuropathy should be kept in mind in clinical practice including diagnostic testing, surgical evaluation, and genetic counseling.