TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome

Manuela Pigors, Dimitra Kiritsi, Cristina Cobzaru, Agnes Schwieger-Briel, Jose Suárez, Flavio Faletra, Heikki Aho, Leeni Mäkelä, Johannes S. Kern, Leena Bruckner-Tuderman, Cristina Has

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Acral peeling skin syndrome (APSS) is an autosomal recessive skin disorder characterized by acral blistering and peeling of the outermost layers of the epidermis. It is caused by mutations in the gene for transglutaminase 5, TGM5. Here, we report on clinical and molecular findings in 11 patients and extend the TGM5 mutation database by four, to our knowledge, previously unreported mutations: p.M1T, p.L41P, p.L214CfsX15, and p.S604IfsX9. The recurrent mutation p.G113C was found in 9 patients, but also in 3 of 100 control individuals in a heterozygous state, indicating that APSS might be more widespread than hitherto expected. Using quantitative real-time PCR, immunoblotting, and immunofluorescence analysis, we demonstrate that expression and distribution of several epidermal differentiation markers and corneodesmosin (CDSN) is altered in APSS keratinocytes and skin. Although the expression of transglutaminases 1 and 3 was not changed, we found an upregulation of keratin 1, keratin 10, involucrin, loricrin, and CDSN, probably as compensatory mechanisms for stabilization of the epidermal barrier. Our results give insights into the consequences of TGM5 mutations on terminal epidermal differentiation.

Original languageEnglish
Pages (from-to)2422-2429
Number of pages8
JournalJournal of Investigative Dermatology
Issue number10
Publication statusPublished - Oct 2012


ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Pigors, M., Kiritsi, D., Cobzaru, C., Schwieger-Briel, A., Suárez, J., Faletra, F., Aho, H., Mäkelä, L., Kern, J. S., Bruckner-Tuderman, L., & Has, C. (2012). TGM5 mutations impact epidermal differentiation in acral peeling skin syndrome. Journal of Investigative Dermatology, 132(10), 2422-2429.