title: Identification of a genetic locus for autosomal dominant disseminated superficial actinic porokeratosis on chromosome 1p31.3-p31.1.
abstract: Disseminated superficial actinic porokeratosis (DSAP) is a chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Two genetic loci for DSAP were identified, but no specific genes were reported to date. The pathogenic mechanism of this disorder remains to be elucidated. In this study, a large, five-generation Chinese family with DSAP was genetically characterized. Two known DSAP loci, DSAP1 and DSAP2, two DSAP candidate genes (SART3 and SSH1), one DSP-linked locus and one PPPD-linked locus were first excluded in the family. The family was then characterized by genome-wide linkage analysis and a new DSAP locus was identified on chromosome 1p31.3-p31.1 with a maximum two-point LOD score of 5.09 with marker D1S2897 (theta = 0). Fine mapping showed that the disease gene was located within an 8.2 cM or 11.9 Mb region between markers D1S438 and D1S464. This is the third locus identified for DSAP (DSAP3). Eight candidate genes including GNG12, IL12RB2, ITGB3BP, DNAJ6, PIN1L, GADD45A, RPE65 and NEGR1 were sequenced, but found to be negative for functional sequence variants. Further mutational analysis of the candidate genes in the region will identify the specific gene for DSAP, which will provide insights into the pathogenesis of DSAP.
authors.affiliation: Key Laboratory of Molecular Biophysics of Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Shouyan
authors.initials: S
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Yao
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Changzheng
authors.initials: C
authors.lastname: Huang
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Huang
authors.forename: Pengyun
authors.initials: P
authors.lastname: Wang
authors.forename: Mingxiong
authors.initials: M
authors.lastname: Yuan
authors.forename: Jing Yu
authors.initials: JY
authors.lastname: Liu
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D020161:Physical Chromosome Mapping; D017499:Porokeratosis / Q000235:genetics*
chemical_list: D005819:Genetic Markers