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

Background: Epidermolytic 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.

Methods: Epidermolytic 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.

Results: Affected 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.

Conclusion: The p.L164P mutation of KRT9 caused EPPK with a novel symptom of palmar constriction. The expression of multiple cytokeratins was altered in EPPK patients.