Collapse of the keratin filament network through the expression of mutant keratin 6c observed in a case of focal plantar keratoderma

Akiharu Kubo, Yuiko Oura, Takashige Hirano, Yumi Aoyama, Showbu Sato, Kaori Nakamura, Yujiro Takae, Masayuki Amagai

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Focal palmoplantar keratoderma (PPK) with severe pain is a hallmark of pachyonychia congenita, a rare autosomal dominant disorder involving PPK and hypertrophic nail dystrophy. Some families present focal PPK with either minimal or no nail changes. Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16 or KRT17, lead to pachyonychia congenita. However, the majority of families with focal PPK showing minimal or no nail changes do not harbor mutations in these genes. Recently, mutations of KRT6C were identified in families with focal PPK alone. Here, we report a 26-year-old Japanese man with focal plantar hyperkeratosis that developed at approximately 10 years of age with no palmar involvement and no nail alterations. We identified a missense KRT6C mutation c.1414G>A resulting in an p.Glu472Lys substitution, as reported in other Japanese patients. When the mutant keratin 6c protein is exogenously expressed in human HaCaT cells, a collapse of the keratin filament network is observed in a dose-dependent manner, suggesting the mutation has a dominant-negative effect on keratin filament network formation. The mutated residue is located at the helix termination motif of keratin 6c. The peptide sequence around this residue is highly conserved among type II, III and IV intermediate filament proteins. Glu to Lys mutations of the equivalent residue have been reported in a variety of inherited diseases, including neurodegenerative diseases, corneal dystrophy and skin disorders, suggesting that this residue is vital to keratin function.

Original languageEnglish
Pages (from-to)553-557
Number of pages5
JournalJournal of Dermatology
Issue number7
Publication statusPublished - 2013 Jul


  • KRT6C
  • intermediate filament proteins
  • keratin 6c
  • pachyonychia congenita
  • palmoplantar keratoderma

ASJC Scopus subject areas

  • Dermatology


Dive into the research topics of 'Collapse of the keratin filament network through the expression of mutant keratin 6c observed in a case of focal plantar keratoderma'. Together they form a unique fingerprint.

Cite this