Firtina Sinem, Saritas Merve, Ng Yuk Yin, Nepesov Serdar, Kiykim Ayca, Bozkurt Selcen, Bilgic-Eltan Sevgi, Ng Ozden Hatirnaz, Sayitoglu Muge
Department of Medical Genetics, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakıf Gureba Cad. No:69, Fatih, Istanbul, 34093, Turkey.
Immunol Res. 2025 May 16;73(1):82. doi: 10.1007/s12026-025-09638-1.
Severe combined immunodeficiency (SCID) represents a life-threatening inborn error of immunity, necessitating rapid diagnosis and intervention to prevent fatal outcomes. While SCID is characterized by profound T-cell lymphopenia, it may overlap with other conditions like ataxia-telangiectasia (AT), which also presents with T-cell deficiencies. This study examines two cases of suspected SCID in infants, later identified as AT due to pathogenic variants in the ATM gene. Despite initial negative results from SCID-targeted gene panels, further genetic testing revealed nonsense mutations (p.Y2036X and p.E1996X) in the FAT domain of the ATM gene, confirmed by Sanger sequencing. The patients exhibited significant T-cell lymphopenia and reduced ATM protein activity, indicative of AT. These findings highlight the importance of comprehensive genetic screening beyond common SCID-associated genes, especially in patients with atypical presentations. Early and accurate diagnosis can prevent mismanagement and guide appropriate therapies, improving patient outcomes.
重症联合免疫缺陷（SCID）是一种危及生命的先天性免疫缺陷病，需要迅速诊断和干预以防止致命后果。虽然SCID的特征是严重的T细胞淋巴细胞减少，但它可能与其他疾病重叠，如共济失调毛细血管扩张症（AT），后者也表现为T细胞缺陷。本研究检查了两例疑似SCID的婴儿病例，后来由于ATM基因的致病变异而被确定为AT。尽管针对SCID的基因检测最初结果为阴性，但进一步的基因检测揭示了ATM基因FAT结构域中的无义突变（p.Y2036X和p.E1996X），经桑格测序证实。患者表现出明显的T细胞淋巴细胞减少和ATM蛋白活性降低，提示为AT。这些发现强调了除常见的SCID相关基因外进行全面基因筛查的重要性，特别是在表现不典型的患者中。早期准确的诊断可以防止管理不当并指导适当的治疗，改善患者预后。
