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

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.

Unusual phenotype of heterozygous LOF mutation in IKZF1, with common variable immunodeficiency presenting initially as immune thrombocytopenia: A case report

“…[12][13][14][15] One case report described a family in which three members (father and two siblings) were diagnosed with the same IKAROS mutation, but presented with a very diverse clinical picture. 16 The index was a female teenager referred by a general practitioner to the paediatrician at the age of 14 for fatigue and recurrent pneumonia complaints, and later diagnosed with CVID. The younger sibling was diagnosed with ITP, while the father was healthy with normal immunoglobulins levels.…”