Tae-Joon Cho, Kazu Matsumoto, and Virginia Fano contributed equally to the work.
Article first published online: 14 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 158A, Issue 4, pages 795–802, April 2012
How to Cite
Cho, T.-J., Matsumoto, K., Fano, V., Dai, J., Kim, O.-H., Chae, J. H., Yoo, W. J., Tanaka, Y., Matsui, Y., Takigami, I., Monges, S., Zabel, B., Shimizu, K., Nishimura, G., Lausch, E. and Ikegawa, S. (2012), TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: A report of three patients. Am. J. Med. Genet., 158A: 795–802. doi: 10.1002/ajmg.a.35268
How to Cite this Article: Cho T-J, Matsumoto K, Fano V, Dai J, Kim O-H, Chae JH, Yoo WJ, Tanaka Y, Matsui Y, Takigami I, Monges S, Zabel B, Shimizu K, Nishimura G, Lausch E, Ikegawa S. 2012. TRPV4-pathy manifesting both skeletal dysplasia and peripheral neuropathy: A report of three patients. Am J Med Genet Part A 158A:795–802.
- Issue published online: 23 MAR 2012
- Article first published online: 14 MAR 2012
- Manuscript Accepted: 16 JAN 2012
- Manuscript Received: 30 JUN 2011
- Ministry for Health, Welfare and Family Affairs, Republic of Korea. Grant Number: A080588
- Ministry of Education, Culture, Sports and Science of Japan. Grant Number: 23390370
- Research on Child Health and Development. Grant Number: 20-3
- Ministry of Health, Labor and Welfare of Japan. Grant Numbers: H22-Nanchi-Ippan-046, H23-Nanchi-Ippan-123
- skeletal dysplasia;
- axonal type peripheral neuropathy
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. © 2012 Wiley Periodicals, Inc.