Mutations in ASPRV1 Cause Dominantly Inherited Ichthyosis.
ASPRV1
Mendelian
SASPase
de novo
dominant
epidermis
exome
ichthyosis
keratoderma
skin
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
02 07 2020
02 07 2020
Historique:
received:
08
01
2020
accepted:
18
05
2020
pubmed:
10
6
2020
medline:
21
10
2020
entrez:
10
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32516568
pii: S0002-9297(20)30160-9
doi: 10.1016/j.ajhg.2020.05.013
pmc: PMC7332602
pii:
doi:
Substances chimiques
FLG protein, human
0
Filaggrin Proteins
0
Intermediate Filament Proteins
0
Aspartic Acid Endopeptidases
EC 3.4.23.-
skin aspartic protease, human
EC 3.4.23.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
158-163Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR068392
Pays : United States
Organisme : NIH HHS
ID : S10 OD018521
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006504
Pays : United States
Informations de copyright
Copyright © 2020 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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