RT Journal Article SR Electronic T1 Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 699 OP 704 DO 10.1136/jmedgenet-2014-102486 VO 51 IS 10 A1 Cui, Hongzhou A1 Li, Longnian A1 Wang, Wenjun A1 Shen, Jie A1 Yue, Zhen A1 Zheng, Xiaodong A1 Zuo, Xianbo A1 Liang, Bo A1 Gao, Min A1 Fan, Xing A1 Yin, Xianyong A1 Shen, Changbing A1 Yang, Chao A1 Zhang, Change A1 Zhang, Xiaoguang A1 Sheng, Yujun A1 Gao, Jinping A1 Zhu, Zhengwei A1 Lin, Da A1 Zhang, Anping A1 Wang, Zaixing A1 Liu, Shengxiu A1 Sun, Liangdan A1 Yang, Sen A1 Cui, Yong A1 Zhang, Xuejun YR 2014 UL http://jmg.bmj.com/content/51/10/699.abstract AB Background Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far. Methods The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene. Results An average of 1.35×105 variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2. Conclusions 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.