259 KLF4 variants: a novel cause of palmoplantar keratoderma

A steadily growing number of hereditary palmoplantar keratodermas (PPKs) have been found to result from defective function epidermal adhesion proteins such as desmoglein 1 (DSG1), a critical component desmosomes which has implicated in the pathogenesis striate, diffuse and focal PPKs. Here we aimed at delineating genetic basis novel dominant form PPK. We studied three patients two families diagnosed with Whole exome sequencing revealed causative pathogenic heterozygous variants KLF4 gene affected individuals. Immunofluorescence staining reduced (DSG1) expression harboring variants. Accordingly, human keratinocytes either transfected constructs expressing these or down-regulated for KLF4, displayed DSG1 expression, previously be associated ChIP assay confirmed direct binding promoter region. The ability mutant trans-activate was significantly decreased. In Conclusion, Loss-of-function cause PPK demonstrate its importance regulation differentiation.