Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A

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.