Functional Assessment of Missense Variants in the ABCC6 Gene Implicated in Pseudoxanthoma Elasticum, a Heritable Ectopic Mineralization Disorder.


Journal

The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720

Informations de publication

Date de publication:
04 2022
Historique:
received: 14 04 2021
revised: 16 08 2021
accepted: 25 08 2021
pubmed: 2 10 2021
medline: 10 5 2022
entrez: 1 10 2021
Statut: ppublish

Résumé

Pseudoxanthoma elasticum, a heritable multisystem ectopic mineralization disorder, is caused by inactivating mutations in the ABCC6 gene. The encoded protein, ABCC6, a transmembrane transporter, has a specialized efflux function in hepatocytes by contributing to plasma levels of inorganic pyrophosphate, a potent inhibitor of mineralization in soft connective tissues. Reduced plasma inorganic pyrophosphate levels underlie the ectopic mineralization in pseudoxanthoma elasticum. In this study, we characterized the pathogenicity of three human ABCC6 missense variants using an adenovirus-mediated liver-specific ABCC6 transgene expression system in an Abcc6

Identifiants

pubmed: 34597610
pii: S0022-202X(21)02224-7
doi: 10.1016/j.jid.2021.08.435
pmc: PMC8957506
mid: NIHMS1744577
pii:
doi:

Substances chimiques

ABCC6 protein, human 0
Abcc6 protein, mouse 0
Diphosphates 0
Multidrug Resistance-Associated Proteins 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1085-1093

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR072695
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR077332
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Luke Kowal (L)

PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Jianhe Huang (J)

PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Hongbin Luo (H)

PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; Department of Dermatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

Jagmohan Singh (J)

Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Adam E Snook (AE)

Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Jouni Uitto (J)

PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

Qiaoli Li (Q)

PXE International Center of Excellence in Research and Clinical Care, Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College, Jefferson Institute of Molecular Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA. Electronic address: Qiaoli.Li@Jefferson.edu.

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Classifications MeSH