Novel TGM5 mutations in acral peeling skin syndrome. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: van der Velden, Jaap J. A. J.; van Geel, Michel; Nellen, Ruud G. L.; Jonkman, Marcel F.; McGrath, John A.; Nanda, Arti; Sprecher, Eli; van Steensel, Maurice A. M.; McLean, W. H. Irwin; Cassidy, Andrew J.
• Is Part Of: Experimental dermatology. Volume 24:Issue 4(2015:Apr.)
• Page Start: 285
• Page End: 289
• Publication Date: 2015-04
• Subjects: acral peeling skin syndrome -- TGM5; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.12650
• Languages: English
• ISSNs: 0906-6705

Abstract

Abstract: Acral peeling skin syndrome (APSS, MIM #609796) is a rare autosomal recessive disorder characterized by superficial exfoliation and blistering of the volar and dorsal aspects of hands and feet. The level of separation is at the junction of the stratum granulosum and stratum corneum. APSS is caused by mutations in the TGM5 gene encoding transglutaminase‐5, which is important for structural integrity of the outermost epidermal layers. The majority of patients originate from Europe and carry a p.(Gly113Cys) mutation in TGM5. In this study, we report both European and non‐European families carrying other mutations in the TGM5 gene. In 5 patients, we found 3 novel mutations: c.1001+2_1001+3del, c.1171G>A and c.1498C>T. To confirm their pathogenicity, we performed functional analyses with a transglutaminase activity assay, determined alternative splicing by reverse‐transcribed PCR analysis and used databases and in silico prediction tools.