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

Background: Porokeratosis is a series of hereditary disorders of epidermal keratinizationcharacterized by an atrophic center surrounded by a slightly raised keratotic border, and atypical histological cornoid lamella. Five clinical variants 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). DSAP is the most common clinical subtype and ischaracterized by multiple uniformly, small, annular, anhidrotic, keratotic lesions over thesun-exposed area. To date, five genetic loci for DSAP (12q23.2-24.1,12q24.1-q24.2,15q25.1-26.1,1p31.3-p31.1and16q24.1-24.3) were found previously. Mutations in SSH1and SART3were identified in two Chinese DSAP families. Recently, Zhang’s groupperformed an exome sequencing in one DSAP family and identified thirteenadditional heterozygous mutations of MVK gene in32%familial DSAP and16%sporadiccases.Objective: Here we performed genetic investigation of five familial and eight sporadicChinese DSAP patients.Methods: Genomic DNA was extracted from the peripheral blood of5probands from5DSAP families,8sporadic cases and100healthy controls. Polymerase chain reaction(PCR)and direct sequencing of the MVK gene were performed to identify and confirm the mutationsin the patients. Results: In sporadic case4, a nonsense mutation in exon3(C.370G>A) was found. Themutation resulted in a premature stop signal at codon62(p.Trp62X), leading to the domaindeletion. In family5, we identified a missense mutation (C.1212T>C), which located in thefourth conserved region. None of these mutations was detected in one hundred controls. Wefailed to detect any mutation of MVK gene in the remaining4DSAP families and7sporadiccases.Conclusion: Two novel mutations were found in5DSAP families and8sporadic cases,which further expand the database of MVK mutations in DSAP, and contribute further to theunderstanding of the pathogenesis of DSAP. This study should be useful for geneticcounseling, prenatal diagnosis and gene therapy for the patients.