A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation
Henry Y. Lu, Robert Sertori, Alejandra Contreras, Mark Hamer, Melina Messing, Kate L. Del Bel, Elena Lopez‐Rangel, Edmond S. Chan, Wingfield Rehmus, Joshua D. Milner, Kelly M. McNagny, Anna Lehman, David L. Wiest, Stuart E. Turvey
Abstract
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.