Keratin K6c mutations cause focal palmoplantar keratoderma

Area of Science:

• Genetics
• Dermatology
• Molecular Biology

Background:

• Palmoplantar keratodermas (PPKs) are a diverse group of genetic skin disorders.
• Existing genetic knowledge for PPKs is incomplete, hindering diagnosis and counseling.
• Mutations in keratin genes KRT6A, KRT6B, KRT16, and KRT17 cause pachyonychia congenita (PC), often with painful focal PPK (FPPK).

Purpose of the Study:

• To identify the genetic cause of familial focal palmoplantar keratoderma (FPPK) in families with minimal nail abnormalities.
• To investigate the role of the KRT6C gene in the etiology of FPPK.

Main Methods:

• Genetic analysis of three unrelated families with familial FPPK.
• Exclusion of mutations in known PC/FPPK-related keratin genes (KRT6A, KRT6B, KRT16, KRT17).
• Mutational analysis of the KRT6C gene.
• Reverse transcription-PCR to confirm KRT6C expression in plantar epidermis.

Main Results:

• No mutations were found in the four known keratin genes.
• Heterozygous in-frame deletion mutations in KRT6C were identified in all three families.
• Identical p.Asn172del mutation in Families 1 and 2; p.Ile462-Glu470del mutation in Family 3.
• KRT6C expression was confirmed in plantar epidermis.

Conclusions:

• Mutations in KRT6C are a novel cause of familial focal palmoplantar keratoderma (FPPK).
• KRT6C mutations expand the genetic basis of palmoplantar keratodermas.
• These findings improve diagnostic capabilities for PPKs.