title: Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3.
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.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Division of Medical Informatics and Bioinformatics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takaoka
authors.affiliation: Division of Medical Informatics and Bioinformatics, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Sugano
authors.affiliation: Department of Clinical Laboratory, Kobe University Hospital, Kobe, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamachi
authors.affiliation: Division of Laboratory Medicine, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawano
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D000328:Adult; D006579:Heterozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D062105:Molecular Docking Simulation; D020125:Mutation, Missense; D035583:Rare Diseases / Q000235:genetics*; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C459445:TRPV3 protein, human
keywords: Olmsted syndrome; TRPV3; in silico analysis; mutation; selectivity filter