Mutation Detection Of MVK Gene With Disseminated Superficial Actinic Porokeratosis

Background:Porokeratosis is characterized by one or more papules or atrophic patches, with an annular appearance surrounded by hyperkeratotic thread-like border that expands centrifugally. It is a rare cutaneous disorder caused by the clonal proliferation of atypical keratinocytes. Disseminated superficial actinic porokeratosis (DSAP) is the most common clinical variant of porokeratosis, and may account for almost half of all cases. Familial cases of DSAP appear to have an autosomal dominant inheritance pattern with high genetic heterogeneity. The mevalonate kinase (MVK) gene has been identified as a candidate gene responsible for DSAP and multiple heterozygous mutations have been reported. They include missense, truncating, and splice site mutations. The MVK gene encodes peroxisomal enzyme mevalonate kinase, which is involved in the biosynthesis of sterol and isoprenoid. Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme. The mevalonate pathway regulates several vital cellular processes, such as cell growth, maturation and formation of cell’s structural framework. Functional studies in keratinocytes suggested that MVK plays a role in regulating calcium-induced keratinocyte differentiation and may protect keratinocytes from ultraviolet (UV) radiation-induced apoptosis.Objective: To detect mutations of MVK gene in two familial patients with disseminated superficial actinic porokeratosis (DSAP). Methods: Polymerase chain reaction and direct sequencing were performed in the 2 DSAP families and 100 healthy controls to identify the mutations of MVK gene.Results: One novel splicing mutation (c.1040-2A>C) and one reported missense mutation (c.1094T>C) were identified. Splice site mutation revealed a mutation at splice donor site of intron 10 which is located two base pair(bp) ahead of exon 11 designated as c.1040-2A> C, leading to the splicing defect. We also detected a heterozygous T to C transition at nucleotide 1094 in exon 11 of MVK gene of the proband (missense mutation). This will result in an amino acid change at codon 364 (p.Phe364Ser), from phenylalanine (TTT) to serine (TCT). We did not detect any mutation in the unaffected family members or the 100 unrelated healthy controls. Conclusions: This study supports that the mutations in MVK gene is associated with the onset of DSAP, which may contribute to the understanding of the pathogenesis of DSAP.