Disseminated superficial actinic porokeratosis (DSAP) is the most common subtype of porokeratosis with genetic heterogeneities, and mevalonate kinase gene (MVK) mutations have been identified in minor portion of DSAP families of Chinese origin.
Disseminated superficial actinic porokeratosis (DSAP) is a severe chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. mevalonate kinase, (MVK) a gene know to play an important role in regulation of calcium-induced keratinocyte differentiation and proliferation, has recently been suggested as the disease-causing gene for DSAP.
A missense mutation (p.Ser63Asn) in SSH1 and a variation (dbSNP3759383: G>A) in the promoter region of ARPC3 were closely linked with DSAP in the pedigree.
A missense mutation (p.Ser63Asn) in SSH1 and a variation (dbSNP3759383: G>A) in the promoter region of ARPC3 were closely linked with DSAP in the pedigree.
Direct DNA sequencing analysis of the whole coding regions of MVK detected three MVK missense mutations, and two were novel for DSAP: c.31C>T (P11S) and c.1004G>A (G335D).
Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK.
Patients with disseminated superficial actinic porokeratosis (DSAP) and linear porokeratosis (LP) exhibit monoallelic germline mutations in genes encoding mevalonate pathway enzymes, such as MVD or MVK.
Primary cultures of keratinocytes and fibroblasts were established from lesional and nonlesional skin biopsies of two subjects with DSAP. p53 mutations were analysed by DNA sequencing of the conserved region of the TP53 gene.
The previous results and this study have shown that DSAP is a genetically heterogeneous disorder; a novel locus for DSAP, termed DSAP2, was mapped to a 6.4-cM region between markers D15S1023 and D15S1030.
The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.
The results indicate that the actinic character of DSAP is not reflected in the cellular response to the lethal effects of UV light, but suggest that DSAP shares X-ray sensitivity, which is probably associated with the cancer-prone nature of PK.