Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing
Abstract Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involve...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Genomic Medicine |
| Online Access: | https://doi.org/10.1038/s41525-024-00453-5 |
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| author | Daniele Merico Nigel Sharfe Harjit Dadi Bhooma Thiruvahindrapuram Jill de Rijke Zakia Dahi Mehdi Zarrei Abdulrahman Al Ghamdi Azhar Al Shaqaq Linda Vong Stephen W. Scherer Chaim M. Roifman |
| author_facet | Daniele Merico Nigel Sharfe Harjit Dadi Bhooma Thiruvahindrapuram Jill de Rijke Zakia Dahi Mehdi Zarrei Abdulrahman Al Ghamdi Azhar Al Shaqaq Linda Vong Stephen W. Scherer Chaim M. Roifman |
| author_sort | Daniele Merico |
| collection | DOAJ |
| description | Abstract Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling. In this study, we describe the role of whole genome sequencing (WGS) in providing a definitive diagnosis for a child with T cell deficiency, where targeted panel sequencing of SCID genes and whole exome sequencing had failed. A novel homozygous 8kb deletion in PTCRA, encoding pTCRα, was identified. To date, use of WGS remains restricted and for many geographical regions, is clinically unavailable. |
| format | Article |
| id | doaj-art-f4705ebc751746b182f80da21f045925 |
| institution | Kabale University |
| issn | 2056-7944 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Genomic Medicine |
| spelling | doaj-art-f4705ebc751746b182f80da21f0459252025-01-19T12:33:35ZengNature Portfolionpj Genomic Medicine2056-79442025-01-0110111110.1038/s41525-024-00453-5Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencingDaniele Merico0Nigel Sharfe1Harjit Dadi2Bhooma Thiruvahindrapuram3Jill de Rijke4Zakia Dahi5Mehdi Zarrei6Abdulrahman Al Ghamdi7Azhar Al Shaqaq8Linda Vong9Stephen W. Scherer10Chaim M. Roifman11The Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoThe Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenThe Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenThe Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenThe Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoThe Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick ChildrenDivision of Immunology and Allergy, Department of Paediatrics, The Hospital for Sick Children and the University of TorontoAbstract Maturation of αβ lineage T cells in the thymus relies on the formation and cell surface expression of a pre-T cell receptor (TCR) complex, composed of TCRβ chain and pre-TCRα (pTCRα) chain heterodimers, giving rise to a diverse T cell repertoire. Genetic aberrations in key molecules involved in T cell development lead to profound T cell immunodeficiency. Definitive genetic diagnosis guides treatment choices and counseling. In this study, we describe the role of whole genome sequencing (WGS) in providing a definitive diagnosis for a child with T cell deficiency, where targeted panel sequencing of SCID genes and whole exome sequencing had failed. A novel homozygous 8kb deletion in PTCRA, encoding pTCRα, was identified. To date, use of WGS remains restricted and for many geographical regions, is clinically unavailable.https://doi.org/10.1038/s41525-024-00453-5 |
| spellingShingle | Daniele Merico Nigel Sharfe Harjit Dadi Bhooma Thiruvahindrapuram Jill de Rijke Zakia Dahi Mehdi Zarrei Abdulrahman Al Ghamdi Azhar Al Shaqaq Linda Vong Stephen W. Scherer Chaim M. Roifman Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing npj Genomic Medicine |
| title | Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing |
| title_full | Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing |
| title_fullStr | Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing |
| title_full_unstemmed | Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing |
| title_short | Pre-T cell receptor-α immunodeficiency detected exclusively using whole genome sequencing |
| title_sort | pre t cell receptor α immunodeficiency detected exclusively using whole genome sequencing |
| url | https://doi.org/10.1038/s41525-024-00453-5 |
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