Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Palmoplantar keratodermas (PPKs) encompass nearly 60 genetic disorders characterized by palm and sole hyperkeratosis.
• Focal PPK is a key feature of pachyonychia congenita, linked to mutations in keratin genes KRT6A, KRT6B, KRT16, or KRT17.
• Recent studies identified KRT6C mutations in families with focal PPK and minimal nail abnormalities.

Observation:

• This study reports a new KRT6C mutation in a Japanese family with PPK exhibiting phenotypic heterogeneity.
• Affected individuals presented with either diffuse sole hyperkeratosis and focal palm lesions or solely focal sole hyperkeratosis.
• All patients were heterozygous for the c.1414G>A mutation in KRT6C, leading to a predicted p.Glu472Lys amino acid change.

Findings:

• A novel KRT6C mutation (c.1414G>A) is identified in a Japanese family with palmoplantar keratoderma (PPK).
• The mutation is associated with phenotypic heterogeneity, ranging from diffuse to focal hyperkeratosis.
• This finding expands the known spectrum of KRT6C-related palmoplantar keratodermas.

Implications:

• Screening for KRT6C mutations should be considered in patients with nonepidermolytic diffuse PPK of unknown genetic cause.
• This research contributes to understanding the genetic basis of palmoplantar keratodermas.
• Identifying novel gene mutations aids in accurate diagnosis and potential therapeutic strategies for genodermatoses.