Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
Department of Biochemistry, Federal Medical & Dental College, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan.
Mol Biol Rep. 2024 Feb 14;51(1):302. doi: 10.1007/s11033-024-09222-0.
Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders.
This current study aims to unwind the molecular etiology of SCID and also extended the patients' phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191) gene.
To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID.
严重联合免疫缺陷症（SCID）是一种常染色体隐性遗传性免疫缺陷病（IEI），其特征为反复发生的胸部和胃肠道（GI）感染，在某些情况下与危及生命的疾病有关。
本研究旨在阐明 SCID 的分子病因，并扩展与已确定特定变异相关的患者表型。在此，我们介绍了在三个不同的 SCID 相关基因中的 07 名 SCID 患者中发现的 06 种致病变异。我们采用外显子组测序（WES）结合 Sanger 测序来探索遗传变异。结果包括首次在 RAG1 基因中以纯合形式发现两个先前报道的杂合变异（p.Arg410Gln；p.Arg737His），随后在 RAG1 中发现了一个反复出现的变异（p.Trp959*），在 IL2RG 中发现了一个新的变异（p.Asp48Lfs24），在 IL2RG 中发现了一个反复出现的变异（p.Gly271Glu），在 DCLRE1C 中发现了一个反复出现的变异（p.Arg191）。
总之，免疫分析和 WES 揭示了两个新的、两个首次以纯合状态存在的、两个导致疾病的反复出现的变异，这些变异为我们现有的 SCID 知识做出了有价值的贡献。
