Identification of a Novel KRT9 Frameshift Mutation in a Chinese Pedigree with Epidermolytic Palmoplantar Keratoderma

Epidermolytic palmoplantar keratodenna (EPPK) is a genodermatosis with autosomal dominant inheritance model. It results from variants of keratin 9 (KRT9) or KRT1 gene. In this study causative gene mapping in a Chinese EPPK family was performed with Two-point linkage analysis and haplotyping. Positive linkage results were obtained on 17q (Zmax-2.06, theta max-0.0) at D17S799, which indicated KRT9 to be the most responsible gene for the family. Subsequently, direct sequencing identified a novel frameshift mutation caused by a 5bp deletion (Delta GGAGG) in KRT9 in all affected individuals but neither in the unaffected subjects nor in the 50 healthy unrelated controls. The frameshift changed the encoding of the following nine amino acids and resulted in a readthrough translation in exon 7. The data revealed that the novel frameshift mutation in KRT9 was responsible for the Chinese EPPK pedigree. The researchers' findings broaden the spectrum of KRT9 variants and provide further evidence for the highly genetic heterogeneity of EPPK.