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Updated: Jun 2, 2025
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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
Published on: January 12, 2021
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Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing
Daniele Merico1,2, Nigel Sharfe3,4, Harjit Dadi3,4
1The Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
NPJ Genomic Medicine
|January 13, 2025
Summary
Whole genome sequencing identified a novel deletion in the PTCRA gene, causing a severe T cell deficiency in a child. This highlights whole genome sequencing
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- T cell maturation in the thymus requires the pre-T cell receptor (TCR) complex, formed by TCRβ and pre-TCRα (pTCRα) chains.
- Genetic defects in T cell development cause severe T cell immunodeficiencies, necessitating accurate genetic diagnosis for treatment and counseling.
Purpose of the Study:
- To investigate the utility of whole genome sequencing (WGS) for diagnosing a child with T cell deficiency when other genetic testing methods failed.
- To identify the specific genetic cause of T cell deficiency in a pediatric patient.
Main Methods:
- Whole genome sequencing (WGS) was employed to analyze the genetic makeup of the patient.
- Targeted panel sequencing and whole exome sequencing were previously performed but did not yield a diagnosis.
Main Results:
- A novel homozygous 8kb deletion in the PTCRA gene, which encodes pTCRα, was identified as the cause of the T cell deficiency.
- This deletion was not detected by prior targeted gene panels or whole exome sequencing.
Conclusions:
- Whole genome sequencing (WGS) can provide a definitive genetic diagnosis for complex T cell deficiencies when standard methods are insufficient.
- The findings underscore the importance of WGS in diagnosing rare genetic disorders, despite its current limitations in clinical availability.
