Linkage And Mutation Analysis Of Gene(s) Associated With Disseminated Superficial Actinic Porokeratosis

Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant skin disorder characterized by numerous annular papules with subtle raised hyperkeratotic borders and slightly atrophic centers, which develops in teenages in sun-exposed areas of skin. Our previous studies showed DSAP was a genetically heterogeneous disorder and identified two loci for the DSAP. DSAP1 was mapped to a 9.6 cM region on chromosome 12q23.2-24.1 with the most likely position between the markers D12S1727 and D12S1605, while DSAP2 was located to a 6.4 cM region between markers D15S1023 and D15S1030 on chromosome 15q25.1-26.1.To confirm those findings, refine the two loci and identify the gene(s) associated with DSAP, genome-wide scan and linkage analysis were carried out in a Chinese DSAP family with 29 members (14 affected and 15 unaffected individuals) of 5 generations. The results establish a linkage of DSAP in this family to chromosome 12q. Further fine mapping and haplotype analysis localized the DSAP locus in this family to a 10.6 cM interval between D12S338 and D12S1341. By comparing with previous findings which showed D12S1605 was at the distal end of DSAP1, DSAP1 could be refined to a 4.4 cM interval between D12S338 and D12S1605 in 12q23.2-q24.1.To identify the disease associated gene for DSAP1, the candidate gene searching was performed. In the 4.4 cM genomic interval between D12S338 and D12S1605 and its flanking regions, 24 potential candidate genes for DSAP1 (AK002128, HCF-2, NFYB, TXNRD1, BC13935, CHST11, SLC41A2, MGC40397, FLJ38508, KIAA1033, DIP13B, ARK5, CKAP4, MGC40368, POLR3B, RFX4, hSyn, MGC17943, LOC80298, CRY1, PWP1, PRDM4, KIAA0789, CMKLR1) , according to information from UCSC and NCBI, and other 11 potential candidate genes ( hCG1793655, hCG1640816, hCG1820714, hCG1820713, hCG1781967, hCG16109, hCG1781850, hCG1820715, hCG16511, hCG16515, hCG1789758) , according to Celera Database, were chosen for further mutation searching. Though we wanted to select as less genes...