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Letter to the Editor| Volume 88, ISSUE 2, P256-258, November 2017

PLACK syndrome resulting from a new homozygous insertion mutation in CAST

Published:June 08, 2017DOI:https://doi.org/10.1016/j.jdermsci.2017.06.004
PLACK syndrome resulting from a new homozygous insertion mutation in CAST
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      Inherited abnormalities of proteases or protease inhibitors have been shown to underlie a spectrum of skin barrier genodermatoses that lead to variable degrees of fragility, scaling and inflammation (reviewed in de Veer et al. [
      • de Veer S.J.
      • Furio L.
      • Harris J.M.
      • Hovnanian A.
      Proteases: common culprits in human skin disorders.
      Trends Mol. Med. 2014; 20: 166-178
      ]). One recent addition to this group is the autosomal recessive disorder, PLACK syndrome (OMIM616295). In 2015, Lin et al. [
      • Lin Z.
      • Zhao J.
      • Nitoiu D.
      • Scott C.A.
      • Plagnol V.
      • Smith F.J.
      • et al.
      Loss-of-function mutations in CAST cause peeling skinleukonychia, acral punctate keratoses, cheilitis, and knuckle pads.
      Am. J. Hum. Genet. 2015; 96: 440-447
      ] reported homozygous loss-of-function mutations in CAST (encoding calpastatin) in three families from different ethnic backgrounds (Chinese, Nepalese and European). Clinically, the signs comprised peeling skin, leukonychia, acral keratoses, cheilitis, and knuckle pads, hence the derivation of the acronym, PLACK syndrome. Calpastatin is an endogenous specific inhibitor of calpain, a calcium-dependent cysteine protease [
      • Potz B.A.
      • Abid M.R.
      • Sellke F.W.
      Role of calpain in pathogenesis of human disease processes.
      J. Nat. Sci. 2016; 2: e218
      ]. It is expressed in most tissues (except brain) with high expression of CAST noted in stratified squamous epithelia, including skin [
      • Potz B.A.
      • Abid M.R.
      • Sellke F.W.
      Role of calpain in pathogenesis of human disease processes.
      J. Nat. Sci. 2016; 2: e218
      ]. Loss of calpastatin in the affected individuals led to defective keratinocyte adhesion as well as increased keratinocyte apoptosis [
      • Lin Z.
      • Zhao J.
      • Nitoiu D.
      • Scott C.A.
      • Plagnol V.
      • Smith F.J.
      • et al.
      Loss-of-function mutations in CAST cause peeling skinleukonychia, acral punctate keratoses, cheilitis, and knuckle pads.
      Am. J. Hum. Genet. 2015; 96: 440-447
      ]. Three different homozygous mutations were reported: c.607dup (p.Ile203Asnfs*8), c.424A >T (p.Lys142*), and c.1750delG (p.Val584Trpfs*37) [
      • Lin Z.
      • Zhao J.
      • Nitoiu D.
      • Scott C.A.
      • Plagnol V.
      • Smith F.J.
      • et al.
      Loss-of-function mutations in CAST cause peeling skinleukonychia, acral punctate keratoses, cheilitis, and knuckle pads.
      Am. J. Hum. Genet. 2015; 96: 440-447
      ]. However, no further reports of PLACK syndrome have been documented thereafter.
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      Article info

      Publication history

      Published online: June 08, 2017
      Received: February 14, 2017

      Identification

      DOI: https://doi.org/10.1016/j.jdermsci.2017.06.004

      Copyright

      © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

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