Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3
Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3
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DOI：
10.1111/1346-8138.13844
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发表时间：
2017-09-01
影响因子：
3.1
通讯作者：
Nishigori, Chikako
中科院分区：
文献类型：
--
作者：
Nagai, Hiroshi;Takaoka, Yutaka;Nishigori, Chikako
奥姆斯特德综合征是一种非常罕见的先天性疾病，其特征是掌跖角化病和周围角化病变。最近，TRPV3被报道为Olmsted综合征的致病基因。我们在一例日本Olmsted综合征患者中发现了TRPV3的杂合错义突变，c.1703G>T，p.Gly568Val。据我们所知，这是第一次报告的日本患者奥姆斯特德综合征窝藏错义突变TRPV3。我们对TRPV3进行了计算机模拟分析，以评价p.Gly568Val是否导致TRPV3选择性过滤器的结构变化。由于基因突变（p.Gly573Ser、p.Tr692Gly或p.Gly568Val）以及温度变化（300 K至310 K），选择性过滤器显示出扩张和高渗透性。TRPV3的计算机分析可能是预测突变诱导的离子通道激活状态的有用方法，从而丰富我们对Olmsted综合征发病机制的理解。
Olmsted syndrome is a very rare congenital disorder, characterized by palmoplantar keratoderma and periorificial keratotic lesions. Recently, TRPV3 was reported to be a causative gene of Olmsted syndrome. We identified a heterozygous missense mutation of TRPV3, c.1703G>T, p.Gly568Val, in a Japanese patient with Olmsted syndrome. To the best of our knowledge, this is the first report of a Japanese patient with Olmsted syndrome harboring a missense mutation in TRPV3. We conducted in silico analysis of TRPV3 to evaluate whether the p.Gly568Val leads to structural changes in the TRPV3 selectivity filter. The selectivity filter was shown to become dilated and hyperpermeable as a result of genetic mutation (p.Gly573Ser, p.Tr692Gly or p.Gly568Val) as well as after a change in temperature (300 K to 310 K). In silico analysis of TRPV3 could be a useful approach in predicting mutation-induced activated states of ion channels, and thus enrich our understanding of the pathogenesis of Olmsted syndrome.