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acral peeling skin syndrome

MIM.609796

Saturday 4 February 2006

Peeling skin syndrome is an autosomal recessive genodermatosis characterized by the shedding of the outer epidermis. In the acral form, the dorsa of the hands and feet are predominantly affected.

Ultrastructure

- tissue separation at the junction between the granular cells and the stratum corneum in the outer epidermis

Etiology

- homozygous mutation in transglutaminase-5 (TGM5) at 15q15.2
(MIM.603805)

  • TG5 is strongly expressed in the epidermal granular cells, where it cross-links a variety of structural proteins in the terminal differentiation of the epidermis to form the cornified cell envelope.
  • An established, in vitro, biochemical cross-linking assay revealed that, although T109M is not pathogenic, G113C completely abolishes TG5 activity.
  • Three-dimensional modeling of TG5 showed that G113C lies close to the catalytic domain, and, furthermore, that this glycine residue is conserved in all known transglutaminases, which is consistent with pathogenicity.
  • protein cross-linking by TG5 is vital for maintaining cell-cell adhesion between the outermost layers of the epidermis.

References

- Cassidy AJ, van Steensel MA, Steijlen PM, van Geel M, van der Velden J, Morley SM, Terrinoni A, Melino G, Candi E, McLean WH. A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome. Am J Hum Genet. 2005 Dec;77(6):909-17. PMID: 16380904

- Candi E, Schmidt R, Melino G. The cornified envelope: a model of cell death in the skin. Nat Rev Mol Cell Biol. 2005 Apr;6(4):328-40. PMID: 15803139