Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Sci Rep. 2022 Mar 8;12(1):4036. doi: 10.1038/s41598-022-08019-0.
Germline ATM gene variations result in phenotypic heterogeneity characterized by a variable degree of disease severity. We retrospectively collected clinical, genetic, and immunological data of 26 cases with A-T. Clinical manifestations included oculocutaneous telangiectasia (100%), ataxia (100%), fever, loose stools or infection (67%), cerebellar atrophy (50%), nystagmus (8%), dysarthria (15.38%), and visual impairment (8%). Genetic analysis confirmed ATM gene variations in 16 unrelated cases. The most common type of variation was stopgain variants (56%). Immunoglobulin profile indicated reduced IgA, IgG, and IgM in 94%, 50%, and 20% cases, respectively. T cell lymphopenia was observed in 80% of cases among those investigated. Unusual presentations included an EBV-associated smooth muscle tumour located in the liver in one case and Hyper IgM syndrome-like presentation in two cases. Increased immunosenescence was observed in T-cell subsets (CD4+CD57+ and CD8+CD57+). T-cell receptor excision circles (TRECs) were reduced in 3/8 (37.50%) cases.
胚系 ATM 基因突变导致表型异质性,表现为疾病严重程度的不同。我们回顾性收集了 26 例 A-T 患者的临床、遗传和免疫学数据。临床表现包括眼皮肤毛细血管扩张症(100%)、共济失调(100%)、发热、稀便或感染(67%)、小脑萎缩(50%)、眼球震颤(8%)、构音障碍(15.38%)和视力障碍(8%)。16 例无亲缘关系的病例经基因分析证实存在 ATM 基因突变。最常见的变异类型是无义变异(56%)。免疫球蛋白谱显示 94%、50%和 20%的病例分别存在 IgA、IgG 和 IgM 减少。在调查的病例中,80%的病例存在 T 细胞淋巴细胞减少症。不常见的表现包括一例 EBV 相关平滑肌肿瘤位于肝脏,两例表现为高 IgM 综合征样。T 细胞亚群(CD4+CD57+和 CD8+CD57+)存在免疫衰老增加。3/8(37.50%)病例的 T 细胞受体切除环(TRECs)减少。