A novel frameshift mutation in keratin 16 underlies pachyonychia congenita with focal palmoplantar keratoderma

Abstract

Funding sources: This work was supported by the National 863 Program of China (2007AA02Z440) and the National Natural Science Foundation of China (81000253 and 30971164). Conflicts of interest: none declared. Madam, Pachyonychia congenita (PC) comprises a group of autosomal dominant genetic disorders that involve ectodermal dysplasia. Historically, two main clinical subtypes of PC have been described, PC‐1 (MIM 167200) and PC‐2 (MIM 167210).1 2–3 PC has been linked to mutations in four keratin genes that are expressed in the epithelia, KRT6A, KRT6B, KRT16 and KRT17.4, 5 Recently, more specific molecular genetic nomenclature has been adopted by the International Pachyonychia Congenita Consortium. In this system, PC‐6a, PC‐6b, PC‐16 and PC‐17 refer to cases with mutation identified in the genes KRT6A, KRT6B, KRT16 and KRT17, respectively. PC‐U designates cases of suspected PC, where either a mutation has not been found or has not been investigated.6, 7 We report a large Chinese pedigree of PC with focal palmoplantar keratoderma. Two‐point linkage analysis and haplotype analysis were carried out to map the disease locus; DNA sequencing and restriction endonuclease analysis were then used to identify the pathogenic mutation.