Analysis Of Clinical And Genetic Features Of 9 Patients With Disseminated Superfacial Actinic Porokeratosis

Background Porokeratosis(PK)is a rare inherited chronic progressive parakeratosis dermatosis.This disease is an autosomal dominant inherited disease that can occur in members of a family for generations,but may also include patients with no genetic evidence.According to morphology,skin lesions distribution,different clinical processes,Clinically,five subtypes of porokeratosis are recognized: classic porokeratosis of Mibelli(PM),Linear porokeratosis(LP),disseminated superficial actinic porokeratosis(DSAP),disseminated superficial porokeratosis(DSP)and Porokeratosis palmariset plantaris disseminata(PPPD).Among of them,DSAP is the most common one.However,the pathogenic genes that cause the disease so far are still not entirely clear.In this study,we tested the gene of DSAP in 1 pedigree and 5 sporadic Han Chinese patients,at the same time we will be analyzed the clinical phenotype and genetic characteristics of DSAP patients.Objective To analyze the clinical phenotype and genetic characteristics of 9 cases of DSAP in Chinese Han population.Method Genomic DNA was extracted from peripheral blood samples from all the patients.Polymerase chain reaction and direct sequencing were performed in five patients in the family and 4 sporadic cases and 120 healthy controls to identify the mutations of MVK,MVD,PMVK,FDPS genes and SLC17A9,SSH1,SART3 genes.Moreover,we reviewed all papers about DSAP related gene mutation of Chinese Han population reported so far.Results One mutations(c.746T>C)was identified in the family and two sporadic cases,and one mutation(c.875A>G)was identified in another sporadic case.All our patients were found no mutations in the other genes.To date 45 pathogenic mutations associated with DSAP in Chinese Han population have been reported.The mutation rates of MVK,MVD,SSH1,SLC17A9,SART3,FPDS genes are 60.3%,27.6%,5.2%,3.4%,1.7%,1.7%,respectively.The mutation rates of c.746T>C and c.875A>G in MVD are 56.3%,25%,respectively;In the aspect of clinical phenotypes,about 96.9%of the skin lesions were located in expose area.Family pedigree were accounted for65.5%.The onset age between 21 and 40 were up to 62.1%.Conclusions This study provided further evidence that mutations in the mevalonate pathway genes are associated with the onset of DSAP in the Chinese Han population,among them with MVK is the most common gene mutations,while MVD is the second,and there are two hot spot mutations c.746 T> C and c 875 A > G;The skin lesions of DSAP are widely distributed in the exposed parts,superficial and disseminated,and rashes are significantly related with sunlight.By analyzing the phenotype in patients in this study,confirmed that rashes have obvious relationship with the sunlight,but there exits significant difference in phenotype among the individuals.