GATA2 deficiency phenotype associated with tandem duplication of GATA2 and overexpression of GATA2-AS1.
GATA2 deficiency phenotype associated with tandem duplication of GATA2 and overexpression of GATA2-AS1.
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DOI：
10.1182/bloodadvances.2021005217
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发表时间：
2021-12-28
期刊：
影响因子：
7.5
通讯作者：
Collin M
中科院分区：
文献类型：
--
作者：
Singh P;Heer M;Resteu A;Mikulasova A;Reza M;Largeaud L;Dufrechou S;Prade N;Dickinson RE;Bustamante J;Neven B;Bigley V;Delabesse E;Rico D;Pasquet M;Collin M
GATA2缺陷的典型特征与GATA2的从头串联重复和GATA2-AS1表达增加相关。重复包含母系遗传的缺失拷贝数多态性esv2725896/nsv513733。一个3岁的女孩，非血缘健康的父母提出了颈部和纵隔淋巴结病由于分枝杆菌偶发感染。常规血液分析显示血红蛋白、中性粒细胞和血小板正常，但单核细胞严重缺乏（单核细胞<0.1 × 109/L; B细胞78/μ L; NK细胞48/μ L）。通过靶向捕获和深度测序对含有GATA 2的548 902 bp区域进行测序。这揭示了整个GATA 2基因座的从头187-kb重复，包含25 kb的母系遗传拷贝数变异缺失（GRCh37：esv2725896和nsv513733）。许多GATA 2相关表型归因于氨基酸取代、移码/缺失、内含子增强子功能丧失或异常剪接。基因缺失已被描述，但在生殖系构型中的其他结构变异尚未报道。在这种情况下，GATA2基因座的重复与GATA2信使RNA表达的偏斜减少和GATA2蛋白的丢失矛盾地相关。未检测到嵌合RNA融合转录物。一种可能的机制涉及反义长非编码RNA GATA2-AS1（RP 11 - 472.220）的转录增加，其增加了数倍。该病例进一步强调，在任何疑似GATA 2相关综合征的病例中，等位基因计数的评估都是必不可少的。
Typical features of GATA2 deficiency were associated with a de novo tandem duplication of GATA2 and increased expression of GATA2-AS1. The duplication contained a maternally inherited deletion copy number polymorphism esv2725896/nsv513733. A 3-year-old girl of nonconsanguineous healthy parents presented with cervical and mediastinal lymphadenopathy due to Mycobacterium fortuitum infection. Routine blood analysis showed normal hemoglobin, neutrophils, and platelets but profound mononuclear cell deficiency (monocytes < 0.1 × 109/L; B cells 78/μL; NK cells 48/μL). A 548 902-bp region containing GATA2 was sequenced by targeted capture and deep sequencing. This revealed a de novo 187-kb duplication of the entire GATA2 locus, containing a maternally inherited copy number variation deletion of 25 kb (GRCh37: esv2725896 and nsv513733). Many GATA2-associated phenotypes have been attributed to amino acid substitution, frameshift/deletion, loss of intronic enhancer function, or aberrant splicing. Gene deletion has been described, but other structural variation has not been reported in the germline configuration. In this case, duplication of the GATA2 locus was paradoxically associated with skewed diminished expression of GATA2 messenger RNA and loss of GATA2 protein. Chimeric RNA fusion transcripts were not detected. A possible mechanism involves increased transcription of the anti-sense long noncoding RNA GATA2-AS1 (RP11-472.220), which was increased several fold. This case further highlights that evaluation of the allele count is essential in any case of suspected GATA2-related syndrome.
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影响因子：
11.4
作者：
Kozyra EJ;Pastor VB;Lefkopoulos S;Sahoo SS;Busch H;Voss RK;Erlacher M;Lebrecht D;Szvetnik EA;Hirabayashi S;Pasaulienė R;Pedace L;Tartaglia M;Klemann C;Metzger P;Boerries M;Catala A;Hasle H;de Haas V;Kállay K;Masetti R;De Moerloose B;Dworzak M;Schmugge M;Smith O;Starý J;Mejstrikova E;Ussowicz M;Morris E;Singh P;Collin M;Derecka M;Göhring G;Flotho C;Strahm B;Locatelli F;Niemeyer CM;Trompouki E;Wlodarski MW;European Working Group of MDS in Childhood (EWOG-MDS)
通讯作者：
European Working Group of MDS in Childhood (EWOG-MDS)
影响因子：
30.5
作者：
Laurenti E;Doulatov S;Zandi S;Plumb I;Chen J;April C;Fan JB;Dick JE
通讯作者：
Dick JE
影响因子：
64.5
作者：
Groeschel, Stefan;Sanders, Mathijs A.;Delwel, Ruud
通讯作者：
Delwel, Ruud
影响因子：
3
作者：
Zhang, L.;Gao, L.;Sun, G. Y.
通讯作者：
Sun, G. Y.
影响因子：
10.1
作者：
Donadieu, Jean;Lamant, Marie;Pasquet, Marlene
通讯作者：
Pasquet, Marlene