title: Acral peeling skin syndrome resulting from a homozygous nonsense mutation in the CSTA gene encoding cystatin A.
abstract: 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.
authors.affiliation: Department of Dermatology, College of Medicine, University of Illinois, Chicago, Illinois.
authors.forename: Aleksandar L
authors.initials: AL
authors.lastname: Krunic
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Stone
authors.forename: Michael A
authors.initials: MA
authors.lastname: Simpson
authors.forename: John A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D001483:Base Sequence; D018389:Codon, Nonsense; D003241:Consanguinity; D055312:Cystatin A / Q000235:genetics*; D003873:Dermatitis, Exfoliative / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D010375:Pedigree; D010859:Pigmentation Disorders / Q000235:genetics* / Q000473:pathology; D012871:Skin Diseases / Q000151:congenital
chemical_list: D018389:Codon, Nonsense; D055312:Cystatin A; C026407:CSTA protein, human