GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity
GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics, and immunity
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DOI：
10.1182/blood-2013-07-515528
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发表时间：
2014-02-06
期刊：
影响因子：
20.3
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Spinner, Michael A.;Sanchez, Lauren A.;Holland, Steven M.
造血转录因子GATA2的单倍体不足导致单核细胞减少和分枝杆菌感染；树突状细胞、单核细胞、B细胞和自然杀伤(NK)淋巴系统缺陷；家族性骨髓增生异常综合征(MDS)/急性髓系白血病(AML)；以及Emberger综合征(伴MDS的原发淋巴水肿症)。目前缺乏对GATA2缺乏症临床特征的全面检查。我们回顾了1992年1月1日至2013年3月1日在美国国立卫生研究院评估的57例GATA2缺乏症患者的医疗记录，并将突变归类为错义、零或调节突变，以确定基因与表型的关联。我们确定了一系列疾病：血液病(MDS 84%，AML 14%，慢性粒单核细胞白血病8%)，感染性(严重病毒70%，播散性分枝杆菌53%，侵袭性真菌感染16%)，肺部(弥漫性79%，呼吸缺陷63%，肺泡蛋白沉着症18%，肺动脉高压9%)，皮肤科(疣53%，脂膜炎30%)，肿瘤(人类乳头瘤病毒+肿瘤35%，Epstein-Barr病毒+肿瘤4%)，血管/淋巴管(静脉血栓形成25%，淋巴水肿11%)，感音神经性听力损失76%，流产33%，甲状腺功能减退14%。病毒感染和淋巴水肿在零突变个体中更常见(分别为P=.038和P=.006)。单核细胞减少症、B淋巴细胞减少症、NK细胞减少症和CD4淋巴细胞减少症与疾病的存在呈正相关(P
Haploinsufficiency of the hematopoietic transcription factor GATA2 underlies monocytopenia and mycobacterial infections; dendritic cell, monocyte, B, and natural killer (NK) lymphoid deficiency; familial myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML); and Emberger syndrome (primary lymphedema with MDS). A comprehensive examination of the clinical features of GATA2 deficiency is currently lacking. We reviewed the medical records of 57 patients with GATA2 deficiency evaluated at the National Institutes of Health from January 1, 1992, to March 1, 2013, and categorized mutations as missense, null, or regulatory to identify genotype-phenotype associations. We identified a broad spectrum of disease: hematologic (MDS 84%, AML 14%, chronic myelomonocytic leukemia 8%), infectious (severe viral 70%, disseminated mycobacterial 53%, and invasive fungal infections 16%), pulmonary (diffusion 79% and ventilatory defects 63%, pulmonary alveolar proteinosis 18%, pulmonary arterial hypertension 9%), dermatologic (warts 53%, panniculitis 30%), neoplastic (human papillomavirus+ tumors 35%, Epstein-Barr virus+ tumors 4%), vascular/lymphatic (venous thrombosis 25%, lymphedema 11%), sensorineural hearing loss 76%, miscarriage 33%, and hypothyroidism 14%. Viral infections and lymphedema were more common in individuals with null mutations (P=.038 and P=.006, respectively). Monocytopenia, B, NK, and CD4 lymphocytopenia correlated with the presence of disease (P