Zhang Zheng-Hu, Niu Zhen-Min, Yuan Wen-Tao, Zhao Jing-Jun, Jiang Fa-Xing, Zhang Jing, Chai Bao, Xiong Xiao-Yan, Xiang Lei-Hong, Wang Yi, Xu Shi-Jie, Liu Wei-Da, Zheng Zhi-Zhong, Huang Wei
Chinese National Human Genome Center at Shanghai and Health Science Center, SIBS, CAS and SSMU, Shanghai 201203, China.
Yi Chuan Xue Bao. 2005 Jul;32(7):667-74.
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.
播散性浅表性光化性汗孔角化症（DSAP）是一种罕见的常染色体显性慢性角化障碍性疾病，其特征为多个浅表角化性损害，周围有轻微隆起的角化性边缘。在以往的研究中，该病基因被定位到12q23.2 - 24.1（DSAP1）和15q25.1 - 26.1（DSAP2）。在本研究中，对两个无关的六代DSAP家系进行了全基因组扫描，以定位和鉴定疾病的候选基因。连锁分析显示，在重组率θ为0.00时，标记D12S84获得的累积最大两点连锁值为8.28。单倍型分析确定了12q24.1 - q24.2上标记D12S330和D12S354之间DSAP基因的一个8.0 cM关键区域，该区域与为DSAP1确定的区域部分重叠。根据六个候选基因（CRY1、PWP1、ASCL4、PRDM4、KIAA0789和CMKLR1）在关键重叠区间的位置，对其编码外显子进行DNA测序，未在DSAP患者中检测到任何突变。因此，这些基因可能不参与DSAP的发病机制。
