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Case Reports
. 2022 Apr 11:13:865838.
doi: 10.3389/fimmu.2022.865838. eCollection 2022.

Case Report: A Highly Variable Clinical and Immunological Presentation of IKAROS Deficiency in a Single Family

Taco W Kuijpers  1   2 , Samantha A M Tromp  1   3 , Ester M M van Leeuwen  3 , Godelieve J de Bree  4
Affiliations
Case Reports

Case Report: A Highly Variable Clinical and Immunological Presentation of IKAROS Deficiency in a Single Family

Taco W Kuijpers et al. Front Immunol. .

Abstract

Here we describe a novel mutation in the IKZF gene encoding IKAROS, as the cause of common variable immunodeficiency (CVID). The identification of the same defect in the IKZF gene with manifestations of asymptomatic selective IgA deficiency and chronic ITP in the father and her younger brother, respectively, demonstrates the large variability of this genetic defect in one single family, while living in the same environment with a relatively similar genetic background. As discussed, clinical penetrance of the molecular defects identified by mutations in IKZF and other common gene defects in CVID in familial immune-related abnormalities makes genetic testing a necessary step for diagnosis, management, and counseling, as part of the routine immunological workup.

Keywords: IKZF1; Ikaros; common variable immunodeficiency (CVID); inborn error of immunity (IEI); whole exome sequencing (WES).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Family tree with the genetically affected members following haploinsufficiency with variable penetrance. The index case is indicated by an arrow, who presented with a typical CVID. (B) The position of the mutation is with an arrow (adapted from Yamashita et al. (7). Mutations comprise early stop codons (red), missense mutations (black), a deletion (blue), and splice defect (green). Larger deletions causing a complete haploinsufficiency have also been described (7). L, low; V, variable; N, normal.
Figure 2
Figure 2
(A) Absolute B-cell, T-cell, and NK-cell numbers. Gray indicates age-dependent normal values. (B) Percentages of naive (CD27-IgD+), non-switched memory (CD27+IgD+), and switched memory B cells (CD27+IgD-) within the total B-cell pool (CD19+CD20+). Gray indicates normal values for adolescents; gray stripe indicates normal values for adults. (C) Representative flow cytometry plots of B-cell subsets. (D) Proliferation of B cells measured by CFSE dilution. (E) IgG production in vitro after 20 days of culture in ng/mL measured by ELISA. (F) IgM production in vitro after 20 days of culture in ng/mL measured by ELISA.
See this image and copyright information in PMC

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