Analysis of the <i><scp>KRT</scp>9</i> Gene in a Mexican Family with Epidermolytic Palmoplantar Keratoderma

López-Valdez, Jaime; Rivera-Vega, M.R.; González-Huerta, Luz María; Cazarín, Jorge; Cuevas-Covarrubias, Sergio A.

doi:10.1111/pde.12027

Cited by 10 publications

(9 citation statements)

References 21 publications

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“…We are not sure whether the palmar constriction was due to merely reduced extension of the thick epidermal plaques, or to involvement of some deeper tissues. Other phenotypes have been reported in some studies such as camptodactyly (23%, Du et al, ; Li et al, ; Liang et al, ; Lopez‐Valdez et al, ; Mao et al, ), nail lesions (Küster et al, ; Liang et al, ), blister (Hennies, Zehender, Kunze, Küster, & Reis, ; Navsaria et al, ), scaling (Warmuth, Cserhalmi‐Friedman, Schneiderman, Grossman, & Christiano, ), hyperhidrosis (Li et al, ), and cosegregation with breast and ovarian cancer (Torchard et al, ). They were not found in our case.…”

Section: Discussionmentioning

confidence: 91%

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Liu

Qiu

et al. 2019

Molec Gen & Gen Med

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BackgroundEpidermolytic palmoplantar keratoderma (EPPK) is characterized by hyperkeratotic lesions on palms and soles. The disorder is caused by mutations of keratin 9 (KRT9) or KRT1 gene.MethodsEpidermolytic palmoplantar keratoderma was diagnosed by physical examination and histopathological analysis in a five‐generation Chinese family. Mutation was screened by Sanger sequencing. The palmar expression of multiple cytokeratins were analyzed by tape‐stripping and Real‐time PCR. Literatures of EPPK with additional symptoms were reviewed.ResultsAffected family members showed diffuse palmoplantar keratosis, with knuckle pads, friction‐related lesions and a novel additional symptom of palmar constriction. A heterozygous mutation of c.T491C (p.L164P) of KRT9 was found within the helix initiation motif. The hydrophobic effect was decreased and the initiation of coiled‐coil conformation was delayed. The KRT16/KRT6 expression were significantly increased in the patients, especially on the right, indicating activation of stress‐response and wound‐healing cytokeratins. There were also increased KRT9/KRT2, unchanged KRT10/KRT1, and undetectable KRT14/KRT5 expression. The genetic and phenotypic heterogeneity of EPPK with additional symptoms were summarized by literature review.ConclusionThe p.L164P mutation of KRT9 caused EPPK with a novel symptom of palmar constriction. The expression of multiple cytokeratins was altered in EPPK patients.

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Section: Discussionmentioning

confidence: 91%

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Liu

Qiu

et al. 2019

Molec Gen & Gen Med

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“…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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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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“…It was first described in 1901 by Vorner. The incidence rate is approximately 2.2 to 4.4 per 100 000 live newborns (Bonifas et al, 1994; Covello et al, 1998; Smith, 2003; Lopez-Valdez et al, 2013; Liu et al, 2014). Some patients may have hyperhidrosis, knuckle pads, camptodactyly and digital mutilation (Lu et al, 2003; Du et al, 2011; Umegaki et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Genetic Analysis of KRT9 Gene Revealed Previously Known Mutations and Genotype-Phenotype Correlations in Epidermolytic Palmoplantar Keratoderma

Tang

Han

et al. 2019

Front. Genet.

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Epidermolytic palmoplantar keratoderma (EPPK, OMIM 144200) is an autosomal dominant inherited disease, clinically characterized by diffuse yellowish thickening of the skin on the palms and soles, usually with erythematous borders developing during the first weeks or months after birth. Pathogenesis of EPPK is determined by mutations in the keratin gene (KRT9). Thirty three mutations in the KRT9 gene from 100 EPPK families have been identified. Among these, 23 mutations are located in the 1A region (a mutation hot spot region), 7 are located in the 2B region, and the remaining 3 are synonymous mutations. In this study, three heterozygous mutations (p.N161S, p.R163W, and p.R163Q), located in regions of the gene encoding the conserved central a-helix rod domain, were detected in the KRT9 gene of the three large Chinese families. This study confirms that codon 163 (48 of 100 cases) is a hot spot mutation site for KRT9. Additional findings identified p.N161S (4%) and p.R163W (4%) as potential hot spot mutations for EPPK associated with knuckle pads, and p.R163Q (15 of 100 cases) as the hot spot mutation of EPPK not occurring in combination with knuckle pads. In conjunction with future studies, this research may help lay the foundation for genetics counseling, prenatal diagnosis and clinical treatment of EPPK.

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Analysis of the KRT9 Gene in a Mexican Family with Epidermolytic Palmoplantar Keratoderma

Cited by 10 publications

References 21 publications

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Keratin 9 L164P mutation in a Chinese pedigree with epidermolytic palmoplantar keratoderma, cytokeratin analysis, and literature review

Epidermolytic Palmoplantar Keratoderma of Vörner-Case Report

Genetic Analysis of KRT9 Gene Revealed Previously Known Mutations and Genotype-Phenotype Correlations in Epidermolytic Palmoplantar Keratoderma

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