Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis

✍ Scribed by Zhenghua Zhang; Zhenmin Niu; Wentao Yuan; Weida Liu; Leihong Xiang; Jing Zhang; Xun Chu; Jingjun Zhao; Faxing Jiang; Bao Chai; Fan Cui; Ying Wang; Kaiyue Zhang; Yi Wang; Shijie Xu; Longqing Xia; Jun Gu; Shoumin Zhang; Xuemei Meng; Shuxia Wang; Shunqiang Gao; Min Fan; Lei Nie; Zhizhong Zheng; Wei Huang

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 440 KB
• Volume: 24
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.9283

✦ Synopsis

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. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP.