期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
卷 158A, 期 4, 页码 795-802出版社
WILEY-BLACKWELL
DOI: 10.1002/ajmg.a.35268
关键词
TRPV4; skeletal dysplasia; axonal type peripheral neuropathy
资金
- Ministry for Health, Welfare and Family Affairs, Republic of Korea [A080588]
- Ministry of Education, Culture, Sports and Science of Japan [23390370]
- Research on Child Health and Development [20-3]
- Ministry of Health, Labor and Welfare of Japan [H22-Nanchi-Ippan-046, H23-Nanchi-Ippan-123]
- German Federal Ministry of Education and Research (BMBF, SKELNET consortium)
- Japanese Skeletal Dysplasia Consortium
- Grants-in-Aid for Scientific Research [23390370] Funding Source: KAKEN
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. (C) 2012 Wiley Periodicals, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据