Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome
Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome
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DOI：
10.1182/blood-2011-05-356352
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发表时间：
2011-09-08
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：
Hsu, Amy P.;Sampaio, Elizabeth P.;Holland, Steven M.
单核细胞减少症、B细胞和NK细胞淋巴细胞减少症以及分枝杆菌、真菌和病毒感染的综合征与骨髓增生异常、细胞遗传学异常、肺泡蛋白沉积症和骨髓性白血病有关。常染色体显性和散发病例均发生。我们确定了影响20名患有该综合征的患者和亲属的12种不同的GATA 2突变，包括影响锌指-2结构域的复发性错义突变（R398 W和T354 M），表明基因功能的显性干扰。四个离散的插入/缺失突变，导致移码和过早终止牵连单倍性不足作为一个可能的作用机制，以及。这些突变在造血和体细胞组织中发现，并且在家庭中鉴定出几种，表明生殖系传播。因此，GATA 2加入RUNX 1和CEBPA不仅作为一个家族性白血病基因，而且作为一个复杂的先天性免疫缺陷的原因，几十年来不断演变，并结合感染和骨髓恶性肿瘤的易感性。（血。2011;118（10）：2653-2655）
The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis, and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recur-rent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant interference of gene function. Four discrete insertion/deletion mutations leading to frame shifts and premature termination implicate haploin-sufficiency as a possible mechanism of action as well. These mutations were found in hematopoietic and somatic tissues, and several were identified in families, indicating germline transmission. Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy. (Blood. 2011;118(10):2653-2655)