Identification of a novel substitution mutation (R103C) in the rod domain of the keratin 17 gene associated with pachyonychia congenita type 2

Pachyonychia congenita (PC) is a rare group of genodermatoses, inherited by autosomal dominant mutations in epithelial specific keratin genes: KRT6A, KRT6B, KRT6C, KRT16, and KRT17. Keratins are major structural proteins in epithelial cell cytoarchitecture where, as heterodimers of keratin I and II, they act as resilient scaffolds that withstand mechanical and non-mechanical stresses. The keratin protein is composed of central alpha-helical rod domain flanked by a head and a tail domain at the Nand Ctermini, respectively. The helical rod domain is divided by linker sequences into 1A, 1B, 2A, and 2B subdomains. Most of the identified keratin genetic defects in PC comprise of missense mutations or small in-frame insertion or deletion mutations, altering the amino acid sequence in the helical boundary motif. The defective keratin protein is able to form heterodimers with the wild-type protein and result in fragility and weakening of the keratin cytoskeleton. In this report, we describe the case of a child with clinical findings of PC, and subsequent gene sequencing analysis that identified a novel mutation in the a-helical rod domain of the KRT17 gene. We also discuss the clinical implication of this mutation on the pathogenesis and progression of PC. Case report