AUTHOR=Lu Henry Y. , Sertori Robert , Contreras Alejandra V. , Hamer Mark , Messing Melina , Del Bel Kate L. , Lopez-Rangel Elena , Chan Edmond S. , Rehmus Wingfield , Milner Joshua D. , McNagny Kelly M. , Lehman Anna , Wiest David L. , Turvey Stuart E. 

TITLE=A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.788278

DOI=10.3389/fimmu.2021.788278

ISSN=1664-3224

ABSTRACT=<p>B-cell lymphoma/leukemia 11B (BCL11B) is a C<sub>2</sub>H<sub>2</sub> 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.</p>