播散性浅表性光线性汗孔角化症DSAP1位点的精细定位和候选基因的突变检测

播散性浅表性光线性汗孔角化症(DSAP)是一种以多个浅表的角化性皮损，边缘轻微嵴状角化性隆起为特征的少见的慢性角化性皮肤病，呈常染色体显性遗传。以往的研究将该病基因定位于12q23．2—24．1区域(DSAP1)和15q25．1-26．1区域(DSAP2)。本研究对2个无关的六代DSAP家系进行了全基因组扫描和连锁分析，结果显示，这2个DSAP家系在D12窝4位点的最高累积LOD值为8．28(θ=0．00)。单倍型分析结果显示，这2个DSAP家系致病基因位于12q24．1-q24．2(D12S330和D12S354)之间8．0cM的区域内。该区域与DSAP1的致病区域部分重叠。对重叠区域内6个候选基因(CRY1，PWP1，ASCL4，PRDM4，KIAA0789和CMKLR1)的编码区进行序列分析，在DSAP病人中未发现突变位点。提示该6个候选基因可能与这2个DSAP家系的发病机理无关。

Refinement of DSAP1 Locus and Mutation Detection for Candidate Genes

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 Iod score of 8.28 was obtained with the marker D12 S84 at a recombination fraction θ of 0.00. Haplotype analysis defined an 8.0 cM critical region for DSAP gene(s) between markers D12 S330 and D12 S354 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.