Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad-like lesions and recurrent mutation causing digital mutilation

Umegaki, Noriko; Nakano, Hajime; Tamai, Katsuto; Mitsuhashi, Yoshihiko; Akasaka, Eijiro; Sawamura, Daisuke; Katayama, Ichiro

doi:10.1111/j.1365-2133.2011.10317.x

Cited by 17 publications

(24 citation statements)

References 8 publications

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“…6 Recently, it has been shown that epidermolytic PPK due to keratin 9 mutation can lead to digital mutilation. The Unna-Thost form of PPK is clinically identical to localized epidermolytic hyperkeratosis of the palms and soles as described by Vorner.…”

Section: Discussionmentioning

confidence: 99%

Unna-Thost type of palmoplantar keratoderma: a case report

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Unna-Thost type of palmoplantar keratoderma: a case report

et al. 2015

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“…Among the seven KRT9 gene mutations identified in the 2B rod domain (including our mutation) [9, 10, 42, 45, 54, 55], five of them are closely distributed, ranging from p.Tyr454 to p.Leu458 [9, 42, 45, 54] (Fig. 4).…”

Section: Discussionmentioning

confidence: 99%

“…The typical clinical feature of EPPK is diffuse yellow keratoses over the entire epidermis of palms and soles, with a well-demarcated erythematous border [7, 8]. Other features are knuckle pads on the digital joints, clubbing of the nails [1], camptodactyly [9], digital mutilation [10], hyperhidrosis, increased sensitivity of the palms and soles to mechanical trauma [1, 11], and decreased heat sensitivity [12]. It usually manifests shortly after birth [7].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Keratin 9 Missense Mutation in a Chinese Family with Epidermolytic Palmoplantar Keratoderma

Xiao

Guo

et al. 2018

Cell Physiol Biochem

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Background/Aims: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant genodermatosis. It is characterized by diffuse yellow keratoses on the palmoplantar epidermis, with an erythematous border. The keratin 9 gene (KRT9) and less frequently the keratin 1 gene (KRT1) are responsible for EPPK. This study aims to identify and analyse genetic defects responsible for EPPK in a Han Chinese pedigree. Methods: A four-generation Han Chinese pedigree containing five individuals affected with EPPK was recruited. Exome sequencing, Sanger sequencing, and bioinformatics tools were conducted to identify the mutation in this pedigree. HaCaT cells were transfected with either wild-type or mutated KRT9. Confocal laser immunofluorescence assay, imaging processing, and statistical analysis were performed to evaluate wild-type and mutant KRT9 groups. Results: A novel heterozygous c.1369C>T transition (p.Leu457Phe) in exon 6 of the KRT9 gene was identified in four patients. It co-segregated with the disorder in the family. Functional analysis showed that withdrawal of the filament network from the cell periphery and particle formation were present in about 10% of Leu457Phe-transfected HaCaT cells, while approximately 3% of cells transfected with wild-type KRT9 showed this phenotype. The particles in mutant group were larger than that in wild-type group (P-value < 0.05). Conclusion: The variant may be the disease-causing missense mutation and produce dominant negative effects by interrupting keratin network formation. This study indicates the pathogenic role of the KRT9 gene mutation in this pedigree with EPPK, and may be helpful in genetic counseling, prenatal diagnosis and gene-targeted therapies of EPPK.

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“…Palmoplantar keratoderma (PPK) comprises a heterogeneous set of hereditary skin diseases caused by genetic mutations in epidermal keratins and has as main manifestation the skin hyperkeratosis of palms and soles, presenting several subtypes that are clinically grouped in three patterns: diffuse, focalized and punctate [5,8,10,11]. Epidermal keratinization disorders occur from genetic modification of the proteins that encode cell envelope, enzymes, adhesion molecules and proteins of the cytoskeleton, and may manifest as keratinizing diseases with the formation of blisters or bullous diseases with hyperkeratosis [11].…”

Section: Discussionmentioning

confidence: 99%

“…It is a rare autosomal dominant genodermatosis, characterized by yellowish and diffuse thickening of the palmar and plantar skin [1,3,7]. It is a unique keratinopathy among keratodermas and the most common diffuse form, usually caused by mutations in keratin (KRT9) and rarely in the keratin 1 gene (KRT1), which is located in chromosome 171 [8,9]. This type of keratin is expressed in suprabasal cells of the epidermis, specifically of palmar and plantar regions [9,10].…”

Section: Introductionmentioning

confidence: 99%

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

Gomides¹,

Felisbino²,

Berbert³

et al. 2018

J Clin Exp Dermatol Res

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Fundaments: Epidermolytic palmoplantar keratoderma (EPPK), Vörner type (EPPK, OMIM 144200), rare autosomal dominant genodermatosis, first described by Vörner in 1901, is the most common form of diffuse keratoderma clinically characterized by the total area of hyperkeratosis on palms and soles. It is usually due to a dominant mutation in the keratin 9 gene (KRT9), located in chromosome 17, which is specific for the palmoplantar skin.Case report: A two-year-old boy presenting hyperkeratosis of palms and soles since the first month of birth. Diffuse hypertrophic plaques with yellowish keratosis and fissures limited to palms and soles, and distinct erythematous margin at the border of normal-appearing skin, were noticed. A punch biopsy of the palms showed epidermolysis in spinous and granular layers, hyperkeratosis and irregular clumped keratohyaline granules.Discussion: EPPK integrates a complex group of uncommon keratodermas, mainly based on the morphologic and topographical characteristics, and associated systemic alteration. It is the most frequent form of such diseases and usually appears during the first weeks or months after birth, characterized by diffuse thickening of the skin of palms and soles with well-circumscribed erythematous borders. This disease may be followed by other ones, above all neoplasias, and probably arises due to segregation of oncogenes. Histopathologically, EPPK presents the characteristic features of epidermolytic hyperkeratosis and vacuolar cytolysis in the upper spinous and granular layers, large irregularly shaped keratohyalin granules and hyperkeratosis, and electron microscopy shows vacuolization of keratinocytes of the granular layer and clumping of keratin filaments. It is differentiated from other palmoplantar keratodermas by the lack of other cutaneous findings and by the presence of histologic features of epidermolytic hyperkeratosis. Currently, there are few therapeutic resources, which are mostly symptomatic. RNA interference strategies are being investigated as an approach to allele-specific gene silencing for dominant-negative keratin diseases.

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Vörner type palmoplantar keratoderma: novel KRT9 mutation associated with knuckle pad-like lesions and recurrent mutation causing digital mutilation

Cited by 17 publications

References 8 publications

Unna-Thost type of palmoplantar keratoderma: a case report

Unna-Thost type of palmoplantar keratoderma: a case report

Identification of a Novel Keratin 9 Missense Mutation in a Chinese Family with Epidermolytic Palmoplantar Keratoderma

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

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