Keratin-9 gene mutation in epidermolytic palmoplantar keratoderma combined with knuckle pads in a large Chinese family

Li, M.; Yang, Lizhu; Hua, Haikang; Zhu, Xiaohong; Dai, Xun-yi

doi:10.1111/j.1365-2230.2007.02384.x

Cited by 11 publications

(9 citation statements)

References 10 publications

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“…The epidermolytic palmoplantar keratoderma Vörner type is a rare genodermatosis with specific histological peculiarities of epidermolytic hyperkeratosis in spinous and granular layers of the epidermis and ultrastructural abnormalities in the keratin intermediate filament network (KIF) and in the grouping of tonofilaments [1,2,10,12]. This KIF stacking pattern occurs due to dominant mutations in the highlyconserved coil 1A region of the KRT9 gene, located in chromosome 17q213 [7,13].…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

“…Therefore, RNA interference strategies are being investigated as an approach for the genetic silencing of specific alleles for dominant negative keratin diseases [10][11][12][13][14][15].…”

Section: Discussionmentioning

confidence: 99%

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

Gomides¹,

Felisbino²,

Berbert³

et al. 2018

J Clin Exp Dermatol Res

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“…We have summarized the cases of EPPK with knuckle pads and documented KRT 9 mutations (Table 1). 7–12 All of these mutations are located in the HIM region, and no correlation with ethnicity has been seen. Although the R163Q mutation of KRT 9 in our case is a recurrent mutation, 2 this is the first case of this mutation with knuckle pads in EPPK.…”

Section: Summary Of Eppk With Knuckle Pads and Detected Krt 9 Mutationmentioning

confidence: 99%

“…Mutant K9 weakens the cytoskeleton and excessive hyperkeratosis occurs in response to mechanical friction 5,6 . Knuckle pads or knuckle pad‐like keratosis may be seen in some patients with EPPK 7–12 . Though mechanical friction and/or a KRT 9 mutation are suggested as its cause, its pathogenesis remains uncertain.…”

Section: Summary Of Eppk With Knuckle Pads and Detected Krt 9 Mutationmentioning

confidence: 99%

Case of epidermolytic palmoplantar keratoderma with knuckle pads

Hayashi

Nakano

Sawamura

et al. 2011

The Journal of Dermatology

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“…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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Keratin-9 gene mutation in epidermolytic palmoplantar keratoderma combined with knuckle pads in a large Chinese family

Cited by 11 publications

References 10 publications

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

Case of epidermolytic palmoplantar keratoderma with knuckle pads

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

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