Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2020 Jun 10

PMID 32516568

Citations 7

Authors

Lynn M Boyden

Jing Zhou

Ronghua Hu

Theodore Zaki

Erin Loring

Jared Scott

Heiko Traupe

Amy S Paller

Richard P Lifton

Keith A Choate

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Evolution of Virus-like Features and Intrinsically Disordered Regions in Retrotransposon-derived Mammalian Genes.

Cagliani R, Forni D, Mozzi A, Fuchs R, Tussia-Cohen D, Arrigoni F Mol Biol Evol. 2024; 41(8).

PMID: 39101471 PMC: 11299033. DOI: 10.1093/molbev/msae154.

Comparative genomics of monotremes provides insights into the early evolution of mammalian epidermal differentiation genes.

Steinbinder J, Sachslehner A, Holthaus K, Eckhart L Sci Rep. 2024; 14(1):1437.

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Epidermal Barrier Development via Corneoptosis: A Unique Form of Cell Death in Stratum Granulosum Cells.

Matsui T J Dev Biol. 2023; 11(4).

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0.5-5% Supramolecular Salicylic Acid Hydrogel is Safe for Long-Term Topical Application and Improves the Expression of Genes Related to Skin Barrier Homeostasis in Mice Models.

Zhou C, Hua C, Liang Q, Al Rudaisat M, Chen S, Song Y Drug Des Devel Ther. 2023; 17:1593-1609.

PMID: 37260764 PMC: 10228590. DOI: 10.2147/DDDT.S397541.

PRSS8, encoding prostasin, is mutated in patients with autosomal recessive ichthyosis.

Shamseldin H, Derar N, Alzaidan H, Alhathal N, Alfalah A, Abdulwahab F Hum Genet. 2023; 142(4):477-482.

PMID: 36715754 DOI: 10.1007/s00439-023-02527-3.

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