端粒生物学障碍可能表现为常见变性免疫缺陷 (CVID)
Benjamin Rolles1, Andres Caballero-Oteyza2, Michele Proietti2
1Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Medical Faculty, RWTH Aachen University, Germany; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD); Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, USA.
端粒维护基因的遗传变异在一些常见变性免疫缺陷 (CVID) 患者中被发现. 这表明CVID可能是端粒生物学障碍 (TBD) 的一部分,影响诊断和治疗.
科学领域:
- 遗传学 遗传学 是一个
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 端粒生物学障碍 (TBD) 源于影响端粒维护的遗传变异,通常呈现出短端粒.
- 成人发病的TBD可能有各种症状,与儿童发病的先天性皮质障碍症 (DC) 相比,诊断复杂化.
- 常见的可变免疫缺陷 (CVID) 是一种主要抗体缺陷 (PAD),伴有低血糖球蛋白血症,B细胞功能障碍和潜在的自身免疫并发症;在15-35%的病例中发现了遗传原因.
研究的目的:
- 在被诊断患有CVID的患者中调查TBD相关遗传变异的流行率.
- 为了评估CVID患者的端粒长度,这些患者携带了端粒维护基因的候选变异.
- 为了确定CVID是否应该被考虑在神秘成人发病TBD的谱中.
主要方法:
- 在491名CVID患者的外体序列测序中,对13个端粒/端粒酶相关基因的变异进行了查.
- 使用ACMG指南对已识别的变种进行分类.
- 选择的CVID患者的淋巴细胞和粒细胞中的端粒长度测量与候选变异.
主要成果:
- 在491名CVID患者中,有110人 (22%) 在研究的基因中携带了91个罕见候选变异.
- 两种变异被归类为致病性/可能致病性,两种VUS在进一步评估后被重新归类为可能致病性.
- 两名患者表现出显著缩短的端粒,所有CVID患者中有0.5-1%携带与端粒相关的基因中的潜在致病变体.
结论:
- 常见变性免疫缺陷 (CVID) 可以呈现为成人开始的端粒生物学障碍 (TBD) 的神秘形式.
- 端粒维护基因的遗传变异存在于CVID患者的一个小但显著的子集中.
- 建议将TBD相关基因纳入抗体缺陷分子查中,以改善诊断和管理.
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