PUBLICATION

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

Authors
Lu, H.Y., Sertori, R., Contreras, A.V., Hamer, M., Messing, M., Del Bel, K.L., Lopez-Rangel, E., Chan, E.S., Rehmus, W., Milner, J.D., McNagny, K.M., Lehman, A., Wiest, D.L., Turvey, S.E.
ID
ZDB-PUB-211214-34
Date
2021
Source
Frontiers in immunology   12: 788278 (Journal)
Registered Authors
Wiest, David
Keywords
BCL11B, hyper IgE, inborn errors of immunity, primary atopic disorders, primary immunodeficiencies
MeSH Terms
  • Adolescent
  • Animals
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Heterozygote
  • Humans
  • Hypersensitivity/diagnosis
  • Hypersensitivity/genetics*
  • Hypersensitivity/immunology
  • Phenotype
  • Primary Immunodeficiency Diseases/diagnosis
  • Primary Immunodeficiency Diseases/genetics*
  • Primary Immunodeficiency Diseases/immunology
  • Primary Immunodeficiency Diseases/metabolism
  • Repressor Proteins/genetics*
  • Repressor Proteins/metabolism
  • Severity of Illness Index
  • T-Lymphocytes/immunology*
  • T-Lymphocytes/metabolism
  • Tumor Suppressor Proteins/genetics*
  • Tumor Suppressor Proteins/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
34887873 Full text @ Front Immunol
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping