Analysis Of MVK Gene Mutations In Chinese Patients With Disseminated Superficial Actinic Porokeratosis

Background: Porokeratosis is a rare hereditary cutaneous disorder of epidermal keratinization, characterized by keratotic lesion with an atrophic center and a distinct peripheral keratotic ridge that corresponds histologically to the cornoid lamella. Clinically, five subtypes of porokeratosis are recognized: disseminated superficial actinic porokeratosis（DSAP）, disseminated superficial porokeratosis（DSP）, classic porokeratosis of Mibelli（PM）, Porokeratosis palmariset plantaris disseminata（PPPD） and Linear porokeratosis（LP）. Among of them, DSAP is the most common one, associated with exposure to sunlight or artificial ultraviolet and characterized by multiple small, minimal, annular, anhidrotic and typical keratotic lesion. DSAP is transmitted in an autosomal-dominant manner with penetrance which is depended with age. Up to date, five susceptible loci have been determined for DSAP, 12q23.2-24.1（DSAP1）, 12q24.1-24.2, 15q25.1-26.1, 1p31.3-p31.1, and 16q24.1-24.3. Moreover, SSH1、 SART3 and MVK genes located in DSAP1 have been identified as the causal genes in DSAP patients.Objective: Here we performed genetic investigation of seven familial and seven sporadic Chinese DSAP patients.Methods: Genomic DNA were extracted from the peripheral blood of seven DSAP families, seven sporadic cases and 100 healthy controls. All the exons of MVK gene and their flanking intronic sequences were amplified by PCR, and then direct sequencing were performed in patients to screen the mutations in the gene.Results: Totally, three missense mutations（c.566C>T、c.722G>T and c.1106C>G） were identified in family 5、family 6 and family 7, respectively. And one frameshift mutation（c.207₂08del AC） in sporadic case 1. None of these mutations were found in 100 controls. Mutations were identified by comparing with reported c DNA reference sequence（Gen Bank accession number: NM₀00431）. We failed to detect any mutation of MVK gene in the remaining 4 DSAP families and 6 sporadic cases.Conclusion: Four novel mutations were found in 7 DSAP families and 7 sporadic cases, which further expand the database of MVK mutations in DSAP. It is noteworthy that we identified a mutation in a DSAP co-existing with PM case, indicating that MVK may be responsible for the pathogenesis of both PM and DSAP. Further investigations and studies are necessary to conducted. This study can useful for genetic counseling, prenatal diagnosis and gene therapy for the patients.