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

Area of Science:

• Genetics
• Neuroscience
• Immunology

Background:

• BCL11B mutations are linked to neurodevelopmental disorders and immunodeficiency.
• Intellectual developmental disorder with speech delay, dysmorphic facies, and T-cell abnormalities (IDDSFTA) and immunodeficiency 49 (IMD49) are associated BCL11B-related conditions.
• The exact pathogenesis and diagnostic strategies for these disorders remain unclear.

Observation:

• A 17-month-old East Asian girl presented with intellectual disability, speech and motor delays, mild dysmorphic features, and abnormal white matter myelination on MRI.
• Immunological analysis revealed normal regulatory T cells (RTEs) and gamma delta T cells (γδT cells) but a deficiency in naive T cells.
• Whole-exome sequencing identified a novel de novo heterozygous frameshift mutation (c.1192_1196delAGCCC) in the BCL11B gene.

Findings:

• The identified mutation in BCL11B is a novel cause of IDDSFTA.
• The patient's presentation expands the known neurological and immunophenotypic spectrum of IDDSFTA.
• This case highlights a specific T-cell deficiency pattern associated with BCL11B mutations.

Implications:

• This research contributes to a better understanding of BCL11B-related disorders.
• Accurate genetic diagnosis is crucial for managing patients with IDDSFTA.
• Further research into BCL11B's role in neurodevelopment and T-cell homeostasis is warranted.