Merico Daniele, Sharfe Nigel, Dadi Harjit, Thiruvahindrapuram Bhooma, de Rijke Jill, Dahi Zakia, Zarrei Mehdi, Al Ghamdi Abdulrahman, Al Shaqaq Azhar, Vong Linda, Scherer Stephen W, Roifman Chaim M
The Centre for Applied Genomics (TCAG), Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Vevo Therapeutics, South San Francisco, CA, USA.
NPJ Genom Med. 2025 Jan 13;10(1):2. doi: 10.1038/s41525-024-00453-5.
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.
αβ谱系T细胞在胸腺中的成熟依赖于前T细胞受体（TCR）复合物的形成和细胞表面表达，该复合物由TCRβ链和前TCRα（pTCRα）链异二聚体组成，从而产生多样化的T细胞库。参与T细胞发育的关键分子的基因畸变会导致严重的T细胞免疫缺陷。明确的基因诊断指导治疗选择和咨询。在本研究中，我们描述了全基因组测序（WGS）在为一名T细胞缺陷儿童提供明确诊断中的作用，该儿童此前进行的重症联合免疫缺陷（SCID）基因靶向panel测序和全外显子组测序均未成功。我们鉴定出了一个位于编码pTCRα的PTCRA基因中的新型纯合8kb缺失。迄今为止，WGS的应用仍然受限，在许多地理区域，临床上无法使用。
