Acral Peeling Skin Syndrome Resulting from a Homozygous Nonsense Mutation in the CSTA Gene Encoding Cystatin A


Address correspondence to John A. McGrath, M.D., F.Med.Sci., Dermatology Research Laboratories, Floor 9, Tower Wing, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK, or e-mail:


Acral peeling skin syndrome (APSS) is a clinically and genetically heterogeneous disorder. We used whole-exome sequencing to identify the molecular basis of APSS in a consanguineous Jordanian-American pedigree. We identified a homozygous nonsense mutation (p.Lys22X) in the CSTA gene, encoding cystatin A, that was confirmed using Sanger sequencing. Cystatin A is a protease inhibitor found in the cornified cell envelope, and loss-of-function mutations have previously been reported in two cases of exfoliative ichthyosis. Our study expands the molecular pathology of APSS and demonstrates the value of next-generation sequencing in the genetic characterization of inherited skin diseases.