A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1.
ferritin
genetics
hyperferritinemia
iron
stabilin-1
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:
03 08 2023
03 08 2023
Historique:
received:
14
02
2023
revised:
29
06
2023
accepted:
06
07
2023
pmc-release:
03
02
2024
medline:
7
8
2023
pubmed:
26
7
2023
entrez:
25
7
2023
Statut:
ppublish
Résumé
Hyperferritinemia is a frequent finding in several conditions, both genetic and acquired. We previously studied eleven healthy subjects from eight different families presenting with unexplained hyperferritinemia. Their findings suggested the existence of an autosomal-recessive disorder. We carried out whole-exome sequencing to detect the genetic cause of hyperferritinemia. Immunohistochemistry and flow cytometry assays were performed on liver biopsies and monocyte-macrophages to confirm the pathogenic role of the identified candidate variants. Through a combined approach of whole-exome sequencing and homozygosity mapping, we found bi-allelic STAB1 variants in ten subjects from seven families. STAB1 encodes the multifunctional scavenger receptor stabilin-1. Immunohistochemistry and flow cytometry analyses showed absent or markedly reduced stabilin-1 in liver samples, monocytes, and monocyte-derived macrophages. Our findings show a strong association between otherwise unexplained hyperferritinemia and bi-allelic STAB1 mutations suggesting the existence of another genetic cause of hyperferritinemia without iron overload and an unexpected function of stabilin-1 in ferritin metabolism.
Identifiants
pubmed: 37490907
pii: S0002-9297(23)00245-8
doi: 10.1016/j.ajhg.2023.07.004
pmc: PMC10432174
pii:
doi:
Substances chimiques
Ferritins
9007-73-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1436-1443Informations de copyright
Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing financial interests.
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