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.

Familial disseminated plaque type porokeratosis with multiple horns and squamous cell carcinoma involving anal skin

“…Recently, another loci has been found within an 8.2 cM or 11.9 Mb region between markers D1S438 and D1S464 (DSAP 3). [3] No gene or genetic locus has been found specifically for Mibelli's type.…”

Exome sequencing identifiesSLC17A9pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis

“…DSAP is transmitted as the autosomal dominant trait. To date, five linkage loci for DSAP reported previously support its heterogeneity (12q23.2–24.1,1 12q24.1–q24.2,2 15q25.1–26.1,3 1p31.3–p31.14 and 16q24.1–24.35). SART3 and SSH1 genes had been identified responsible for different DSAP families 2 6.…”

Disseminated superficial actinic porokeratosis co-existing with linear and verrucous porokeratosis in an elderly woman: Update on the genetics and clinical expression of porokeratosis

“…22,23 DSAP2 (SSH1 and ARPC3 on chromosome 15q25.1-26.1), 24,25 and DSAP3 (on chromosome 1p31.3-p31.1). 26 One potential locus is identified for disseminated superficial porokeratosis (on chromosome 18p11.3) 27 and one for porokeratosis palmaris et plantaris disseminata (on chromosome 12q24.1-24.2). 28 SART3 (squamous cell carcinoma antigen recognized by T cells) is an RNA-binding nuclear protein that can induce HLArestricted and tumor-specific and cytotoxic T cells.…”