Mutant BCL11B in a Patient With a Neurodevelopmental Disorder and T-Cell Abnormalities

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.

Keywords: BCL11B; developmental disorder; immune system abnormalities; immunodeficiency; neurodevelopmental disease.

Figure 1

Clinical features of the patient. (A) The patient presented with facial dysmorphic features with hypertelorism, long philtrum, and thin upper lip vermilion. (B) Axial T1W1 magnetic resonance imaging (MRI) of the patient displayed blotch and piece-like lesions with the prolonged signal. (C) Axial T2W1 MRI imaging of the patient showed the abnormal shades distributed in bilateral frontal, temporal, parietal, and occipital lobes and basal ganglia. (D) From axial FLAIR imaging, the abnormal lesion was identified mainly in the white matter, and strip-like signals can also be observed in the bilateral basal ganglia.

Figure 2

The mutation of BCL11B. (A) Immune cell analysis of the patient indicated lymphopenia. (B) Mutation c.1192_1196delAGCCC was only identified in a patient (shadow shows the chaos of subsequent sequence), but her parents displayed regular sequences. (C) The schema of the BCL11B gene with the frameshift mutation of this study.