Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3. Issue 9 (9th April 2017)

• Record Type: Journal Article
• Authors: Nagai, Hiroshi; Takaoka, Yutaka; Sugano, Aki; Nakamachi, Yuji; Kawano, Seiji; Nishigori, Chikako
• Is Part Of: Journal of dermatology. Volume 44:Issue 9(2017)
• Page Start: 1059
• Page End: 1062
• Publication Date: 2017-04-09
• Subjects: in silico analysis -- mutation -- Olmsted syndrome -- selectivity filter -- TRPV3; Dermatology -- Periodicals; Dermatology -- Japan -- Periodicals; Skin -- Diseases -- Periodicals; 616.5005
• DOI: 10.1111/1346-8138.13844
• Languages: English
• ISSNs: 0385-2407

Abstract

Abstract: 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.