ClinVar

In 3 affected members of a Japanese family with focal or diffuse palmoplantar keratoderma (PPKNEFD; 615735), Wilson et al. (2010) identified heterozygosity for a c.1414G-A transition in exon 7 of the KRT6C gene, resulting in a glu472-to-lys (E472K) substitution at a conserved residue in the C terminus of the 2B domain. The mutation, which segregated with disease in the family, was not found in 104 controls.

In a father and daughter with focal plantar keratoderma, Kubo et al. (2013) sequenced the candidate gene KRT6C and identified heterozygosity for the E472K mutation, which was not present in an unaffected son. Palmar skin as well as the nails of hands and feet were normal in the affected individuals. Analysis of transfected HaCaT cells showed that cells expressing low levels of mutant protein exhibited no alterations in the keratin filament network, whereas cells expressing high levels displayed a collapsed network of keratin filaments. Semiquantification of exogenously expressed KRT6C confirmed that the collapse of the keratin filament network occurred in a manner dependent on the level of expression of mutant keratin-6c.