Abstract
B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger transcription factor that is critically important for regulating the development and function of a variety of systems including the central nervous system, the skin, and the immune system. Germline heterozygous variants are associated with a spectrum of clinical disorders, including severe combined immunodeficiency as well as neurological, craniofacial, and dermal defects. Of these individuals, ~50% present with severe allergic disease. Here, we report the detailed clinical and laboratory workup of one of the most severe BCL11B-dependent atopic cases to date. Leveraging a zebrafish model, we were able to confirm a strong T-cell defect in the patient. Based on these data, we classify germline BCL11B-dependent atopic disease as a novel primary atopic disorder.
Highlights
Primary atopic disorders (PADs) are a group of monogenic disorders that present with dysregulated allergic effector responses (1)
The potentially pathogenic NM_138576:c.2487G>A;NP_612808: p.Cys826Tyr BCL11B variant was selected because (i) germline BCL11B variants have been associated with both neurodevelopmental disorders as well as atopic disease; (ii) it is absent in population databases; and (iii) it is predicted to be pathogenic by a variety of in silico pathogenicity prediction tools
We report one of the most severe atopic cases of BCL11B deficiency to date and the first known Canadian patient. This is the first patient with germline BCL11B variants associated with immune dysregulation/autoimmunity
Summary
Primary atopic disorders (PADs) are a group of monogenic disorders that present with dysregulated allergic effector responses (1). Major clinical features include severe atopic dermatitis, food allergies, allergic asthma, urticaria, eosinophilia, and elevated IgE. Due to the heterogeneous presentation of PADs, it can often be difficult to differentiate monogenic from polygenic etiologies. B-cell lymphoma/leukemia 11B (BCL11B) is a C2H2 zinc finger (ZF) transcription factor protein that is broadly expressed and is important in regulating the development of various tissues, including the central nervous system, T cells, skin, and teeth (2).
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