Premium
Identification of a heterozygous p.Gly568Val missense mutation in the TRPV 3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV 3
Author(s) -
Nagai Hiroshi,
Takaoka Yutaka,
Sugano Aki,
Nakamachi Yuji,
Kawano Seiji,
Nishigori Chikako
Publication year - 2017
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.13844
Subject(s) - missense mutation , trpv , palmoplantar keratoderma , mutation , genetics , gene mutation , in silico , medicine , gene , biology , transient receptor potential channel , receptor , trpv1
Olmsted syndrome is a very rare congenital disorder, characterized by palmoplantar keratoderma and periorificial keratotic lesions. Recently, TRPV 3 was reported to be a causative gene of Olmsted syndrome. We identified a heterozygous missense mutation of TRPV 3 , 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 TRPV 3 . We conducted in silico analysis of TRPV 3 to evaluate whether the p.Gly568Val leads to structural changes in the TRPV 3 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 TRPV 3 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.