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

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

10 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

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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, ~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 = "Publisher Copyright: 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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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

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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 - Repressor Proteins/genetics

KW - Severity of Illness Index

KW - T-Lymphocytes/immunology

KW - Tumor Suppressor Proteins/genetics

KW - Zebrafish Proteins/genetics

KW - Zebrafish/genetics

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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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