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

Henry Y. Lu; Robert Sertori; Alejandra V. 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; Stuart E. Turvey

doi:10.3389/fimmu.2021.788278

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

Henry Y. Lu
, Robert Sertori
, Alejandra V. 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
, Stuart E. Turvey

University of British Columbia
Fox Chase Cancer Center
Columbia University
Department of Pediatrics, British Columbia Children’s Hospital, The University of British Columbia
Temple University

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English
Article number	788278
Pages (from-to)	788278
Journal	Frontiers in Immunology
Volume	12
DOIs	https://doi.org/10.3389/fimmu.2021.788278
State	Published - Nov 23 2021

Keywords

Adolescent
Animals
DNA Mutational Analysis
Female
Genetic Predisposition to Disease
Germ-Line Mutation
Heterozygote
Humans
Hypersensitivity/diagnosis
Phenotype
Primary Immunodeficiency Diseases/diagnosis
Repressor Proteins/genetics
Severity of Illness Index
T-Lymphocytes/immunology
Tumor Suppressor Proteins/genetics
Zebrafish Proteins/genetics
Zebrafish/genetics

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10.3389/fimmu.2021.788278

Cite this

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., & Turvey, S. E. (2021). A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation. Frontiers in Immunology, 12, 788278. Article 788278. https://doi.org/10.3389/fimmu.2021.788278

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title = "A Novel Germline Heterozygous BCL11B Variant Causing Severe Atopic Disease and Immune Dysregulation",

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, \textasciitilde{}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.",

keywords = "Adolescent, Animals, DNA Mutational Analysis, Female, Genetic Predisposition to Disease, Germ-Line Mutation, Heterozygote, Humans, Hypersensitivity/diagnosis, Phenotype, Primary Immunodeficiency Diseases/diagnosis, Repressor Proteins/genetics, Severity of Illness Index, T-Lymphocytes/immunology, Tumor Suppressor Proteins/genetics, Zebrafish Proteins/genetics, Zebrafish/genetics",

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

note = "Copyright {\textcopyright} 2021 Lu, Sertori, Contreras, Hamer, Messing, Del Bel, Lopez-Rangel, Chan, Rehmus, Milner, McNagny, Lehman, Wiest and Turvey.",

year = "2021",

month = nov,

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doi = "10.3389/fimmu.2021.788278",

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journal = "Frontiers in Immunology",

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AU - Wiest, David L.

AU - Lu, Henry Y.

AU - Sertori, Robert

AU - Contreras, Alejandra V.

AU - Hamer, Mark

AU - Messing, Melina

AU - Del Bel, Kate L.

AU - Lopez-Rangel, Elena

AU - Chan, Edmond S.

AU - Rehmus, Wingfield

AU - Milner, Joshua D.

AU - McNagny, Kelly M.

AU - Lehman, Anna

AU - Turvey, Stuart E.

PY - 2021/11/23

Y1 - 2021/11/23

N2 - 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.

AB - 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.

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KW - Animals

KW - DNA Mutational Analysis

KW - Female

KW - Genetic Predisposition to Disease

KW - Germ-Line Mutation

KW - Heterozygote

KW - Humans

KW - Hypersensitivity/diagnosis

KW - Phenotype

KW - Primary Immunodeficiency Diseases/diagnosis

KW - Repressor Proteins/genetics

KW - Severity of Illness Index

KW - T-Lymphocytes/immunology

KW - Tumor Suppressor Proteins/genetics

KW - Zebrafish Proteins/genetics

KW - Zebrafish/genetics

UR - https://www.scopus.com/pages/publications/85120861668

U2 - 10.3389/fimmu.2021.788278

DO - 10.3389/fimmu.2021.788278

M3 - Article

C2 - 34887873

SN - 1664-3224

VL - 12

SP - 788278

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 788278

ER -

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

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

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