[Refinement of DSAP1 locus and mutation detection for candidate genes].

Abstract

Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder,characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. In previous studies,the disease gene was mapped to 12q23. 2-24.1 (DSAP1), and 15q25. 1-26.1 (DSAP2). In this study,genome-wide scan was performed in two unrelated six-generation DSAP pedigrees to localize and identify the candidate gene(s) of disease. Linkage analysis showed that the cumulative maximum two-point lod score of 8.28 was obtained with the marker D12S84 at a recombination fraction theta of 0.00. Haplotype analysis defined an 8.0 cM critical region for DSAP gene(s) between markers D12S330 and D12S354 on 12q24. 1-q24. 2, which partially overlapped with the region identified for DSAP1. DNA sequencing of the coding exons of six candidate genes (CRY1, PWP1, ASCL4, PRDM4, KIAA0789 and CMKLR1) on the basis of their location in the critical overlap interval, failed to detect any mutation in DSAP patients. Thus, it is likely that these genes are not involved in DSAP.