Identification Of A Novel Mutation In The K6a Gene Of Pachyonychia Congenita Type 1

Background Pachyonychia congenita (PC) is an autosomal dominant disorder that usually develops in early infancy. The major features of the syndrome are hypertrophic nail dystrophy, palmoplantar keratoderma and oral leucokeratosis, accompanied by other ectodermal defects, according to subtype. Specifically, PC-1 has been shown to be caused by mutations in keratins K6a and K16. In contrast, PC-2 has been associated with mutations in K6b and K17. K6/K16 are co-expressed in a number of differentiated epithelial structures, including palmoplantar epidermis, mucosal epithelia, follicular keratinocytes and nail bed; whereas K17 is expressed in the pilosebaceous unit and basal appendageal keratinocytes. To date, over 20 mutations in the K6a and K16 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 PC. In the present study, we have ascertained an Chinese patient with PC-1, and examined the K6a and K16 genes mutation by direct sequencing.Objective To analyze the K6a gene mutation in a sporadic Chinese patient with PC-1 and to explore the relationship between the genetype and phenotype of PC-1. Methods Genomic DNA was extracted from peripheral blood of the patient with PC-1 and 100 unrelated normal persons. The whole coding region of the K6a gene was amplified using long-range polymerase chain reaction (PCR), then nested PCR were used to amplify the mutation 'hot-spot' of the K6a gene. The PCR products were directly sequenced to detect the mutation.