Long-term follow up of families with pathogenic <em>NFKB1</em> variants reveals incomplete penetrance and frequent inflammatory sequelae
Tuovinen, Elina A.; 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. (2022-11-08)
Tuovinen, E. A., Kuismin, O., Soikkonen, L., Martelius, T., Kaustio, M., Hämäläinen, S., Viskari, H., Syrjänen, J., Wartiovaara-Kautto, U., Eklund, K. K., Saarela, J., Varjosalo, M., Kere, J., Hautala, T., & Seppänen, M. R. J. (2023). Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae. In Clinical Immunology (Vol. 246, p. 109181). Elsevier BV. https://doi.org/10.1016/j.clim.2022.109181
© 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe20231002138131
Tiivistelmä
Abstract
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.
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