A novel IKZF1 variant in a family with autosomal dominant CVID A case for expanding exon coverage in inborn errors of immunity

A novel IKZF1 variant in a family with autosomal dominant CVID : A case for expanding exon coverage in inborn errors of immunity

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 264(2024) vom: 11. Juni, Seite 110244
1. Verfasser: Stojkic, Ivana (VerfasserIn)
Weitere Verfasser: Prince, Benjamin T, Kuehn, Hye Sun, Gil Silva, Agustin A, Varga, Elizabeth A, Rosenzweig, Sergio D, Ramadesikan, Swetha, Supinger, Rachel, Marhabaie, Mohammad, Chang, Peter, Mardis, Elaine R, Koboldt, Daniel C
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Case Reports CVID IKZF1 Ikaros Transcription Factor 148971-36-2 IKZF1 protein, human
Beschreibung
Zusammenfassung:Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.
Common variable immune deficiency (CVID) is a heterogenous group of disorders characterized by varying degrees of hypogammaglobulinemia, recurrent infections, and autoimmunity. Currently, pathogenic variants are identified in approximately 20-30% of CVID cases. Here we report a 3-generation family with autosomal dominant Common Variable Immunodeficiency (CVID) diagnosed in 9 affected individuals. Although primary immune deficiency panels and exome sequencing were non-diagnostic, whole genome sequencing revealed a novel, pathogenic c.499C > T: p.His167Tyr variant in IKZF1, a critical regulator of B cell development. Functional testing done through pericentromeric heterochromatin localization and light shift chemiluminescent electrophoretic mobility shift assay confirmed the variant's deleterious effect via a haploinsufficiency mechanism. Our findings expand the spectrum of known IKZF1 mutations and contribute to a more comprehensive understanding of CVID's genetic heterogeneity. Furthermore, this case underscores the importance of considering whole genome sequencing for comprehensive genetic diagnosis when concern for a monogenic inborn errors of immunity is high
Beschreibung:Date Completed 14.06.2024
Date Revised 28.06.2024
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2024.110244