Hereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Hereditary palmoplantar keratodermas (PPK) are rare skin disorders characterized by epidermal hyperkeratosis.
• Over 69 genes are linked to PPK, yet novel genes and mutations require identification.

Purpose of the Study:

• To identify genetic mutations underlying PPK in a cohort of 64 patients.
• To investigate the genetic basis of different PPK subtypes.

Main Methods:

• DNA analysis using a custom panel of 35 PPK genes for 48 patients.
• Whole-exome sequencing, gene panels, or targeted sequencing for the remaining 16 patients.

Main Results:

• Pathogenic mutations were found in 48% (31/64) of patients, primarily in AQP5, SERPINB7, KRT9, SLURP1, and AAGAB.
• Diffuse PPK was the most frequent subtype (50%); no striate PPK cases were observed.
• Novel mutations in KRT9 and AAGAB were identified, while no mutations were found in focal PPK cases.

Conclusions:

• Genetic mutations account for nearly half of hereditary palmoplantar keratoderma cases.
• AQP5, AAGAB, KRT9, SERPINB7, and SLURP1 are key genes associated with PPK.
• Further research is needed to understand variants of uncertain significance and unexplained PPK cases.