Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 246(2023) vom: 15. Jan., Seite 109181
1. Verfasser: Tuovinen, Elina A (VerfasserIn)
Weitere Verfasser: Kuismin, Outi, Soikkonen, Leila, Martelius, Timi, Kaustio, Meri, Hämäläinen, Sari, Viskari, Hanna, Syrjänen, Jaana, Wartiovaara-Kautto, Ulla, Eklund, Kari K, Saarela, Janna, Varjosalo, Markku, Kere, Juha, Hautala, Timo, Seppänen, Mikko R J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2023
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Autoinflammation Common variable immunodeficiency Hypogammaglobulinemia Inborn errors of immunity NFKB1 NF-kappa B NF-kappa B p50 Subunit NFKB1 protein, human
Beschreibung
Zusammenfassung:Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Nuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary
Beschreibung:Date Completed 15.02.2023
Date Revised 15.02.2023
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2022.109181