Abstract

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.

Highlights

  • Epidermolytic palmoplantar keratoderma (EPPK, OMIM 144200) is an autosomal dominant genodermatosis that manifests as hyperkeratosis confined to the palms and soles (Reis et al, 1994)

  • Mutations of keratin 9 (KRT9) associated with EPPK usually occur in the helix initiation motif (HIM) or in the 1A rod domain close to HIM

  • We reported a novel symptom of palmar constriction in a Chinese EPPK pedigree in this study

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Summary

| INTRODUCTION

Epidermolytic palmoplantar keratoderma (EPPK, OMIM 144200) is an autosomal dominant genodermatosis that manifests as hyperkeratosis confined to the palms and soles (Reis et al, 1994). KRT9 is exclusively expressed in the suprabasal layers of palmoplantar epidermis, and is essential for maintaining mechanical integrity of palmoplantar epidermis. It is structurally composed of a central rod α‐helical domain, flanked by non‐helical head and tail domains. Mutations of KRT9 associated with EPPK usually occur in the helix initiation motif (HIM) or in the 1A rod domain close to HIM. Another less‐often candidate of EPPK is the KRT1 gene belonging to type II keratin family on chromosome 12q13 (Hatsell et al, 2001). We showed for the first time that heterozygous p.L164P mutation of KRT9 associated with altered expression of multiple cytokeratins in EPPK patients

| MATERIALS AND METHODS
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| DISCUSSION
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