Identification of a heterozygous p.Gly568Val missense mutation in the <i><scp>TRPV</scp>3</i> gene in a Japanese patient with Olmsted syndrome: <i>In silico</i> analysis of <scp>TRPV</scp>3

Nagai, Hiroshi; Takaoka, Yutaka; Sugano, Aki; Nakamachi, Yuji; Nishigori, Chikako

doi:10.1111/1346-8138.13844

Cited by 11 publications

(9 citation statements)

References 14 publications

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“… 10 Indeed, a brazillian OS patient with p.Gly568Val showed mild phenotype such as focal and mild keratodermas, whereas a Japanese case and our patient harboring the same mutation presented diffuse and severe symptoms. 10 11 These findings suggest a possibility that additional genetic modifiers or environmental factors may affect the phenotype.…”

Section: Discussionmentioning

confidence: 91%

“… 3 Mutations at codon 568, like our case, have been reported in only four OS cases so far; the heterozygous missense mutations at p.Gly568Val and p.Gly568Asp and a splice site mutation at p.Gly568Cys. 9 10 11 The amino acid Gly568 also resides within the linker between S4–S5, but near the boundary of S4 and is highly conserved across several species. 10 Previous in silico analysis confirmed that the same amino acid substitution in TRPV3 identified in our patient renders the selectivity filter of this ion channel more hyperpermeable.…”

Section: Discussionmentioning

confidence: 99%

“… 10 Previous in silico analysis confirmed that the same amino acid substitution in TRPV3 identified in our patient renders the selectivity filter of this ion channel more hyperpermeable. 11 Therefore, this variant can be classified as pathogenic (PS1). 12 …”

Section: Discussionmentioning

confidence: 99%

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Olmsted Syndrome Caused by a Heterozygous p.Gly568Val Missense Mutation in TRPV3 Gene

2018

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Olmsted syndrome (OS) is a rare congenital skin disorder characterized by severe palmoplantar and periorificial keratoderma, alopecia, onychodystrophy, and severe pruritus. Recently, pathogenic ‘gain-of-function‘ mutations of the transient receptor potential vanilloid 3 gene (TRPV3), which encodes a cation channel involved in keratinocyte differentiation and proliferation, hair growth, inflammation, pain and pruritus, have been identified to cause OS. Due to the rarity, the pattern of inheritance of OS is still unclear. We report a case of OS in a 3-year-old Korean girl and its underlying gene mutation. The patient presented with a disabling, bilateral palmoplantar keratoderma with onychodystrophy. She also exhibited pruritic eczematous skin lesions around her eyes, ears and gluteal fold. Genetic analysis identified a heterozygous p.Gly568Val missense mutation in the exon 13 of TRPV3. To our knowledge, this is the first case of OS in the Korean population showing a missense mutation p.Gly573Ser.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Olmsted Syndrome Caused by a Heterozygous p.Gly568Val Missense Mutation in TRPV3 Gene

2018

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“…Gain-of-function mutations in human TRPV3 from patients with Olmsted syndrome (OS) suggest a role of TRPV3 in human itch signaling [104]. OS is a rare skin disease characterized by palmoplantar, alopecia, onychodystrophy, and severe itching [105].…”

Section: Trp Channels and Itch Signalingmentioning

confidence: 99%

TRP Channels as Drug Targets to Relieve Itch

Xie

2018

Pharmaceuticals

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Although acute itch has a protective role by removing irritants to avoid further damage, chronic itch is debilitating, significantly impacting quality of life. Over the past two decades, a considerable amount of stimulating research has been carried out to delineate mechanisms of itch at the molecular, cellular, and circuit levels. There is growing evidence that transient receptor potential (TRP) channels play important roles in itch signaling. The purpose of this review is to summarize our current knowledge about the role of TRP channels in the generation of itch under both physiological and pathological conditions, thereby identifying them as potential drug targets for effective anti-itch therapies.

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“…The in silico approach based on structural biology has recently become a powerful tool for molecular pathological analysis (Nagai et al 2017 ; Nakano et al 2014 ; Ogasawara et al 2016 ). We also used this method recently to investigate the effect of TTR prophylactic efficacy (Mu et al 2015 ; Qiang et al 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis

et al. 2017

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The disease model of familial amyloidotic polyneuropathy—7.2-hMet30 mice—manifests amyloid deposition that consists of a human amyloidogenic mutant transthyretin (TTR) (TTR V30M). Our previous study found amyloid deposits in 14 of 27 7.2-hMet30 mice at 21–24 months of age. In addition, non-fibrillar TTR deposits were found in amyloid-negative 7.2hMet30 mice. These results suggested that TTR amyloidogenesis required not only mutant TTR but also an additional factor (or factors) as an etiologic molecule. To determine the differences in serum proteome in amyloid-positive and amyloid-negative mice in the 7.2-hMet30 model, we used proteomic analyses and studied serum samples obtained from these mice. Hemopexin (HPX) and transferrin (Tf) were detected in the serum samples from amyloid-positive mice and were also found in amyloid deposits via immunohistochemistry, but serum samples from amyloid-negative mice did not contain HPX and Tf. These two proteins were also not detected in non-fibrillar TTR deposits. In addition, in silico analyses suggested that HPX and Tf facilitate destabilization of TTR secondary structures and misfolding of TTR. These results suggest that HPX and Tf may be associated with TTR amyloidogenesis after fibrillogenesis in vivo.

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Identification of a heterozygous p.Gly568Val missense mutation in the TRPV3 gene in a Japanese patient with Olmsted syndrome: In silico analysis of TRPV3

Cited by 11 publications

References 14 publications

Olmsted Syndrome Caused by a Heterozygous p.Gly568Val Missense Mutation in TRPV3 Gene

Olmsted Syndrome Caused by a Heterozygous p.Gly568Val Missense Mutation in TRPV3 Gene

TRP Channels as Drug Targets to Relieve Itch

Co-precipitation molecules hemopexin and transferrin may be key molecules for fibrillogenesis in TTR V30M amyloidogenesis

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