Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis

Lynn M. Boyden, Jing Zhou, Ronghua Hu, Theodore Zaki, Erin Loring, Jared Scott, Heiko Traupe, Amy S. Paller, Richard P. Lifton, Keith A. Choate*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


The discovery of genetic causes of inherited skin disorders has been pivotal to the understanding of epidermal differentiation, function, and renewal. Here we show via exome sequencing that mutations in ASPRV1 (aspartic peptidase retroviral-like 1) cause a dominant Mendelian disorder featuring palmoplantar keratoderma and lamellar ichthyosis, a phenotype that has otherwise been exclusively recessive. ASPRV1 encodes a mammalian-specific and stratified epithelia-specific protease important in processing of filaggrin, a critical component of the uppermost epidermal layer. Three different heterozygous ASPRV1 missense mutations in four unrelated ichthyosis kindreds segregate with disease and disrupt protein residues within close proximity to each other and autocatalytic cleavage sites. Expression of mutant ASPRV1 proteins demonstrates that all three mutations alter ASPRV1 auto-cleavage and filaggrin processing, a function vital to epidermal barrier integrity.

Original languageEnglish (US)
Pages (from-to)158-163
Number of pages6
JournalAmerican journal of human genetics
Issue number1
StatePublished - Jul 2 2020


  • ASPRV1
  • Mendelian
  • SASPase
  • de novo
  • dominant
  • epidermis
  • exome
  • ichthyosis
  • keratoderma
  • skin

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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