Name: Combined immunodeficiency with skin-hair depigmentation | Acronym: IRF4-DN
Alt. names: Early-onset PAD with T cell anomalies and skin-hair depigmentation | Hypogammaglobulinemia, T cell abnormalities and skin-hair depigmentation

Gene: IRF4 | MOI: Autosomal dominant | Mechanism of action: Negative Dominance

No. of cases in DB: 4 | First reported in: 2023

Last updated on: 2024-10-25 16:39:55 by Xiao P. Peng

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Thouenon et al. (2023) described a heterozygous neomorphic IAD domain variant (c.1075 T>C, p.(F359L)) in 3 patients from a 2-generation family who presented with hypogammaglobulinemia and early onset recurrent bacterial, viral and fungal infections, predominantly sinorespiratory, GI and mucocutaneous, as well as skin and hair depigmentation (PMID: 36917008). One patient developed TNF inhibitor-responsive inflammatory bowel disease and liver disease with evidence of prominent CD8+ T cell infiltration on pathology. Despite normal overall B cell counts and normal proportions of switched memory B cells in adulthood, all patients had lower proportions of immature T and B cell populations in the blood – namely, reduced naïve vs memory T cells and reduced plasmablast/plasma cell counts. Two patients also showed absolute T cell lymphopenia. Defective IRF4 mutant protein showed altered binding at ISRE, which leads to defective plasma cell differentiation.

Description of management option has not been reviewed yet.