Mutation Analysis Of KRT9 Gene In A Chinese Family With Epidermolytic Palmoplantar Keratoderma

Background Epidermolytic palmoplantar keratoderma (EPPK,OMIM:144200) is an autosomal dominant inherited skin disorder of keratinization. It is characterized by well-demarcated, symmetric hyperkeratosis of the palms and soles associated with histologic findings of hyperkeratosis and epidermolysis (ballooning degeneration) starting in the spinous layer. The onset of the disease is usually during infancy or early childhood. Ultrastructurally, there is vacuolization of the cytoplasm and abnormal keratin filament network characterized by tonofilament clumping. It was first described by Vorner in 1901 and the gene for EPPK was mapped to chromosome 17q12-q21 by linkage analysis by Reis in 1992. In 1994, KRT9 gene was identified and a mutation R162W was identified in a familie with EPPK. Recent molecular studies have shown that EPPK is caused by mutations in KRT9 gene. K9 belongs to the typeâ… keratin which is only expressed in the epidermis of the palms and soles. KRT9 gene contains 8 exons, while just the first to the seventh exon encod 623 amino acids of KRT9 gene. To date, 20 mutations in KRT9 gene have been identified,the majority of these mutations are missense mutations. Comparison between genotype and phenotype failed to yield any clear correlation between the nature of the mutation and the clinical features of EPPK.Objective To analyze the gene mutation of KRT9 gene in a Chinese family with epidermolytic palmoplantar keratoderma and to explore the correlation between the genotypes and phenotypes and to investigate the still-unknow mechanism.Methods (1)A Chinese family with epidermolytic palmoplantar keratoderma was investigated. All the coding exons of KRT9 gene were amplified by polymerase chain reaction and products were analyzed by direct sequencing. The results were compared with that of the other 14 normal members from the same family and 100 unrelated population-matched control individuals. (2)We searched for case reports and papers about DPPK and EPPK since 1980 by Chinese Biology Medicine(CBM)disc and summarized the genetic and clinical features.Results (1)Six patients with EPPK in this family showed a point mutation at nucleotide 485(G>A)compared with that of the normal controls,resulting in the substitution of glutamine for arginine at codon 162.Meanwhile the mutation was not found in the 14 normal individuals and 100 unrelated control samples. (2)The inherited pattern of DPPK was autosomal dominant. There was a marked variability in disease expression not only between families but also within a family. (3)There is no association between genotypes and phenotypes of EPPK reported .Conclusions (1)The c.485G>A mutation of KRT9 gene seemed to be the pathologic cause of this Chinese family with EPPK. (2)The clinical manifestation of patients with DPPK was similarity to some degree, but the expressivity of the disease was obviously variability. (3)A clear correlation between genotypes and phenotypes of EPPK has not been found.