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

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

doi:10.3389/fimmu.2021.788278

Cited by 10 publications

(13 citation statements)

References 13 publications

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“…In our patient, we noticed that the number and percentage of eosinophils and the IgE values of our patient significantly increased. Interestingly, five cases with a high level of eosinophils were also reported by Lessel et al and Lu et al (17,18). Lu and associates proposed this germline BCL11Brelated atopic disease as a novel primary atopic disorder (PAD).…”

Section: Discussionmentioning

confidence: 69%

“…In a summary of the neurodevelopment disorder phenotype of all reported patients (8,9,(17)(18)(19)(20)(21)(22)(23), four were reported to present with abnormal MRI, exhibiting moderate ectopia of the amygdala (17), hypoplasia of the globus pallidus (17), callosal agenesis (8), or an abnormal myelination pattern of white matter 10.3389/fped.2022.982361 (23). Our patient had brain morphological abnormalities with brain asymmetry and affected growth of the right brain.…”

Section: Discussionmentioning

confidence: 81%

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Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Zhao

Chen

et al. 2022

Front. Pediatr.

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Craniosynostosis is a premature fusion of cranial sutures, resulting in abnormally shaped skull and brain development disorder. The description of craniosynostosis in patients with BCL11B mutations is rare. Here, we firstly report a 25-month-old Chinese boy with a novel frameshift variant in BCL11B gene. The patient was identified c.2346_2361del by whole-exome sequencing and was confirmed to be de novo by parental Sanger sequencing. This patient presented clinical phenotype of craniosynostosis as well as global developmental delay. He had a small mouth, thin upper lip, arched eyebrows, a long philtrum, midfacial hypoplasia and craniosynostosis. Brain MRI showed brain extracerebral interval and myelination changes, and brain CT with 3D reconstruction showed multi-craniosynostosis. Our study expands the clinical phenotypes of patients with BCL11B gene mutation, and our findings may help guide clinical treatment and family genetic counseling.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 81%

Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Zhao

Chen

et al. 2022

Front. Pediatr.

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“…Zebrafish LOF atm mutants exhibited similar phenotypes, with multi-lineage immunodeficiency along with motor disturbances and cancer predisposition [ 75 ]. Finally, human BCL11B gain-of-function (GOF) mutations have been identified in an autosomal-dominant syndrome characterized by reduced T cells, congenital craniofacial abnormalities and neurocognitive defects [ 76 ], with overexpression of a patient-derived BCL11B mutant in bcl11b KD zebrafish embryos able to model the T cell defects and dominant nature of the human disease [ 44 ]. Other mutations impact human thymus development and thereby cause immunodeficiency indirectly by abrogating T cell production at this site [ 77 ].…”

Section: Zebrafish Models Of Lymphoid Disordersmentioning

confidence: 99%

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

Basheer

Sertori

Liongue

et al. 2023

IJMS

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Primary immunodeficiency (PID) disorders, also commonly referred to as inborn errors of immunity, are a heterogenous group of human genetic diseases characterized by defects in immune cell development and/or function. Since these disorders are generally uncommon and occur on a variable background profile of potential genetic and environmental modifiers, animal models are critical to provide mechanistic insights as well as to create platforms to underpin therapeutic development. This review aims to review the relevance of zebrafish as an alternative genetic model for PIDs. It provides an overview of the conservation of the zebrafish immune system and details specific examples of zebrafish models for a multitude of specific human PIDs across a range of distinct categories, including severe combined immunodeficiency (SCID), combined immunodeficiency (CID), multi-system immunodeficiency, autoinflammatory disorders, neutropenia and defects in leucocyte mobility and respiratory burst. It also describes some of the diverse applications of these models, particularly in the fields of microbiology, immunology, regenerative biology and oncology.

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“…Zebrafish functional experiments revealed that a BCL11B variant caused human multisystem anomalies with SCID and that BCL11B was crucial in hematopoietic progenitors (Punwani et al, 2016 ). Subsequently, successive reports demonstrated the pathogenicity of BCL11B variants (Alfei et al, 2021 ; Lessel et al, 2018 ; Lu et al, 2021 ; Prasad et al, 2020 ; Qiao et al, 2019 ; Yang et al, 2020 ). All patients presented with developmental delay, most of whom presented with intellectual disability, mild facial dysmorphisms, and impaired T‐cell development.…”

Section: Introductionmentioning

confidence: 99%

A novel variant in BCL11B in an individual with neurodevelopmental delay: A case report

Yang

Jia

Yin

et al. 2023

Molec Gen & Gen Med

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Background B‐Cell CLL/Lymphoma 11B (BCL11B) is a C 2 H 2 zinc finger transcription factor that has broad biological functions and is essential for the development of the immune system, neural system, cardiovascular system, dermis, and dentition. Variants of BCL11B have been found in patients with neurodevelopmental disorders and immunodeficiency. Materials and Methods Whole‐exome sequencing (WES) and clinical examinations were performed to identify the etiology of our patient. A variant in the BCL11B gene, NM_138576.4: c.1206delG (p.Phe403Serfs*2) was found and led to frameshift truncation. Results We reported a male patient with developmental delay and cerebral palsy who carried the BCL11B variant. The detailed clinical features, such as brain structure and immune detection, were described and reviewed in comparison to previous patients. Conclusions The BCL11B‐related neurodevelopmental disorders are rare, and only 17 variants in 25 patients have been found to date. Our report expands the variants spectrum of BCL11B and increases the case of neurodevelopmental abnormalities.

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

Cited by 10 publications

References 13 publications

Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Case report: A novel truncating variant of BCL11B associated with rare feature of craniosynostosis and global developmental delay

Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?

A novel variant in BCL11B in an individual with neurodevelopmental delay: A case report

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