Identification Of Three Novel Frameshift Mutations Of The MVK Gene In Four Chinese Families With Disseminated Superficial Actinic Porokeratosis

Background: Porokeratosis is a group of hereditary disorders of epidermalkeratinization, characterized by keratotic lesions with an atrophic centre andprominent peripheral ridge, and a typical histological cornoid lamella. There areseveral clinical subtypes of porokeratosis, including disseminated superficial actinicporokeratosis (DSAP), disseminated superficial porokeratosis (DSP), classicporokeratosis of Mibelli (PM), Porokeratosis palmariset plantaris disseminata (PPPD)and Linear porokeratosis(LP), all of whom show typical pathological manifestations:cornoid lamella in the epidermis. Among of them, DSAP as the most commonclinical subtype of porokeratosis, has been widely studied to identify the geneticvariance. Up to date, four genetic loci have been mapped to be responsible for DSAP,12q23.2-24.1(DSAP1),15q25.1-26.1(DSAP2),1p31.3-p31.1(DSAP3), and16q24.1-24.3(DSAP4). SSH1, SART and MVK genes located in DSAP1have beenidentified as the causal genes in Chinese DSAP patients.Objective: Here we performed genetic investigation of ten familial and four sporadicChinese DSAP patients.Methods: Genomic DNA was extracted from the peripheral blood of14affectedindividuals and2unaffected individuals from10DSAP families,4sporadic cases and 100healthy controls. Polymerase chain reaction(PCR) and direct sequencing of theMVK gene were performed to identify and confirm the mutations in the patients.Results: The frameshift mutations of c.395delT(exon5), c.853insA(exon9),c.1057del TGGAGG CCACGAAG (exon11) was identified in Family1, Family2,Sporadic1, Sporadic2, respectively. Among of them, the case of Family1andFamily2have the same mutation (c.395delT).None of these mutations was found inunaffected family members and100controls.Conclusion: Three novel frameshift mutations were found in10DSAP families,4sporadic cases, which further expand the database of MVK mutations in DSAP. It isintriguing that we also detected mutations of MVK gene in two DSAP co-existingwith PM cases, which indicates that PM and DSAP may both result from the mutationof MVK gene. This study should be useful for genetic counseling, prenatal diagnosisand gene therapy for the patients.