Date: 06/12/2020

Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis


Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis

Published:June 08, 2020DOI:


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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.



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Article Info

Publication History

Published: June 8, 2020

Accepted: May 18, 2020

Received: January 8, 2020

Publication stage

In Press Corrected Proof




© 2020 American Society of Human Genetics.


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