Abstract
Background: BCL11B encodes B-cell lymphoma/leukemia 11B, a transcription factor that participates in the differentiation and migration of neurons and lymphocyte cells. De novo mutations of BCL11B have been associated with neurodevelopmental disorder and immunodeficiency, such as immunodeficiency 49 (IMD49) and intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA). However, the pathogenesis of the neurodevelopmental disorder and T-cell deficiency is still mysterious. The strategy to distinguish these two diseases in detail is also unclear.Methods: A patient with unique clinical features was identified. Multiple examinations were applied for evaluation. Whole-exome sequencing (WES) and Sanger sequencing were also performed for the identification of the disease-causing mutation.Results: We reported a 17-month-old girl with intellectual disability, speech impairment, and delay in motor development. She presented with mild dysmorphic facial features and weak functional movement. MRI indicated the abnormal myelination of the white matter. Immunological analysis showed normal levels of RTEs and γδT cells but a deficiency of naive T cells. Genetic sequencing identified a de novo heterozygous frameshift mutation c.1192_1196delAGCCC in BCL11B.Conclusions: An IDDSFTA patient of East Asian origin was reported. The unreported neurological display, immunophenotype, and a novel disease-causing mutation of the patient extended the spectrum of clinical features and genotypes of IDDSFTA.
Highlights
BCL11B gene encodes the transcription factor B-cell leukemia, which regulates the differentiation, proliferation, and apoptosis of T lymphocytes
Naive CD4+/CD8+ T cells were defined as CD3+CD45RA+CD62L+ cells in the CD4+/CD8+ subset, and recent thymic emigrants (RTEs) were defined as CD45RA+CD31+ cells in the CD4+ subset. γδ T cells were defined as T cells with a positive T-cell receptor (TCR)-γδ signal
The patient was 85 cm in height [−2 standard deviation (SD)], 11 kg in weight (−2 SD to −1 SD) and 47 cm in head circumference (−1 SD) at 29 months
Summary
BCL11B gene encodes the transcription factor B-cell leukemia, which regulates the differentiation, proliferation, and apoptosis of T lymphocytes. The encoded protein, BCL11B, is a zinc finger transcription factor that modulates T-cell receptors through regulating the DNA-binding transcription to direct the migration of hematopoietic progenitors [1] It monitors the development of group 2 innate lymphoid cells. Immunodeficiency 49 (IMD49) is the first identified congenital disease caused by BCL11B mutations, characterized by severe immunodeficiency with dysmorphic features, skin abnormalities, and global developmental delay. Intellectual developmental disorder with speech delay, dysmorphic facial features, and T-cell abnormalities (IDDSFTA) is a newly identified type of BCL11B-associated congenital malformation, which overlaps with IMD49 in some features including feeding difficulties and autistic features [7]. De novo mutations of BCL11B have been associated with neurodevelopmental disorder and immunodeficiency, such as immunodeficiency 49 (IMD49) and intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA). The strategy to distinguish these two diseases in detail is unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
