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Disruption of TCBA1 associated with a de novo t(1;6)(q32.2;q22.3) presenting in a child with developmental delay and
1Institute for Human Genetics, Johannes Gutenberg University, Mainz, Germany.
Insights
A novel t(1;6) translocation disrupts the TCBA1 gene, leading to developmental delay and distinct facial features in a young boy. This finding links TCBA1 gene alterations to neurodevelopmental disorders.
Area of Science:
- Genetics
- Developmental Biology
- Oncology
Background:
- A balanced de novo translocation t(1;6)(q32.3;q22.3) was identified in a boy with developmental delay, distinctive facial features, antineutrophil cytoplasmic antibodies, and recurrent infections.
- The translocation breakpoints were precisely mapped using advanced molecular techniques, including fluorescent in situ hybridization (FISH) and long-range PCR.
Observation:
- The chromosome 1 breakpoint was located within a hypothetical gene, LOC388735.
- The chromosome 6 breakpoint occurred within intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene.
- TCBA1 gene disruption and potential fusion gene formation were observed in T-cell lymphoma and leukemia cell lines, suggesting its role in tumorigenesis.
Findings:
- The study identified TCBA1 as a gene potentially involved in both tumorigenesis and developmental disorders.
- The mouse Tcba1 gene shares high sequence similarity with human TCBA1 and is expressed in the brain, liver, and testes.
- Human TCBA1 expression is reported in the brain and thymus; reduced expression in these tissues may correlate with the patient's symptoms.
Implications:
- Germline alterations in the TCBA1 gene are associated with developmental delay and characteristic physical features.
- This research highlights TCBA1 as a potential candidate gene for neurodevelopmental disorders and provides insights into its role in T-cell malignancies.
- Further investigation into TCBA1 function and expression patterns is warranted to fully understand its contribution to disease pathogenesis.
Abstract:
A boy with developmental delay, particularly of speech, a distinct face, antineutrophil cytoplasmic antibodies, and recurrent infections was found to have an apparently balanced de novo t(1;6)(q32.3;q22.3) translocation. Fluorescent in situ hybridisation with BAC/PAC clones and long range polymerase chain reaction products assessed in the human genome sequence localised the chromosome 1 breakpoint to a 9.8 kb segment within a hypothetical gene, LOC388735, and the chromosome 6 breakpoint to a 12.8 kb segment in intron 4 of the T-cell lymphoma breakpoint-associated target 1 (TCBA1) gene. Disruption and/or formation of TCBA1 fusion genes in T cell lymphoma and leukaemia cell lines suggests a role for this gene in tumorigenesis. The isolated mouse Tcba1 gene shows 91% amino acid sequence similarity with human TCBA1. It is expressed in fetal and adult brain and with lower levels in liver and testis. The human gene has been reported to be expressed exclusively in brain and thymus. Reduced TCBA1 expression in brain and thymus may explain at least some of the symptoms in this patient. It is concluded that germline alterations of the TCBA1 gene are associated with developmental delay and typical physical features.
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