测试ID：GATA2
GATA-Binding Protein 2 (GATA2), Full Gene, Next-Generation Sequencing, Varies

全面评估GATA2具有临床或免疫症状的患者的基因，暗示了GATA结合蛋白2（GATA2）缺乏症

筛查确认GATA2缺乏症患者的家庭成员

该测试包括下一代测序和补充Sanger测序。

病原变异的鉴定可以帮助预后，临床管理，家族筛查和遗传咨询。

For skin biopsy or cultured fibroblast specimens,fibroblast culture and cryopreservation testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

在常见的可变免疫缺陷（CVID）之后，GATA结合蛋白2（GATA2）缺乏症已成为成年人中第二常见的原发性免疫缺陷障碍（PIDD）或先天误差。与GATA2缺乏相关的临床表现范围很广，包括严重的病毒感染（例如，人乳头瘤病毒：HPV），疣，疣，真菌感染，细菌感染（例如，非链分枝杆菌感染，如无链分枝杆菌感染或鸟分枝杆菌[MAC]），骨髓脱发综合征（MDS），急性髓样白血病和伴有伴随的lympheympheymeme（MD）。GATA2缺乏症的其他临床表型可能包括性贫血，肺肺泡蛋白质病，感觉神经性听力丧失，中性粒细胞减少症和先天性淋巴水肿，没有MDS诊断。免疫学表型包括树突状细胞，单核细胞，CD4+ T细胞，B-和天然杀手 - （NK）细胞缺陷。同样，这些患者已经报道了特定的NK细胞子集CD56明亮NK细胞的丢失。GATA2缺乏症在2011年首次被描述为与Monomac（单核细胞减少症和分枝杆菌感染）综合征或DCML缺乏症（树突状细胞，单核细胞，B和NK细胞淋巴细胞缺乏症）有关。

GATA2 is a zinc finger transcription factor, involved in the generation and function of hematopoietic stem cell progenitors and, therefore, affects several of the subsequent cell lineages.

GATA2缺乏症是一种单倍不足的疾病，大多数种系变体似乎是从头出现的（自发），但随后以常染色体显性方式传播。标准的基因型 - 表型相关性很难建立，因为存在相当大的临床异质性，并且表现的年龄从幼儿期到成年后期的差异。此外，环境因素可能会触发某些传染性表现。观察到GATA2缺乏症和可变表达性（同一遗传变异的不同临床表现）观察到的不完全的外渗（并非每个具有变体的人都有临床表型）。GATA2是异质的，包括内含子5的调节区域中的错义变体，胡说八道的变体和变体，涉及C末端锌指域的框内删除，移交式变体和大型缺失。后者与无效等位基因相关，而在内含子5的增强子区域已经观察到调节变体。

Somatic variants inasxl1已经报道了GATA2缺乏症的患者，并被认为与转化为髓样白血病有关。GATA2缺乏的明确治疗方法是造血细胞移植（HCT）。此外，全身使用干扰素-Alpha可能对患有复发性或严重HPV或疱疹病毒感染的NK细胞缺乏症患者有帮助。同样，在非移植患者中可能需要或要求预防性抗生素。在GATA2缺乏症中观察到的肺肺泡蛋白质病在抗GM-CSF自身抗体的阴性结果是HCT后改善的，并表明校正了肺泡巨噬细胞功能。

Early genetic diagnosis of GATA2 deficiency is critical in determining strategies for managing the disease considering the broad clinical spectrum. Genetic diagnosis by confirmation of a pathogenicGATA2变体还可以帮助家庭咨询和筛查。

An interpretive report will be provided.

使用最新出版的美国医学遗传学和基因组学学院（ACMG）建议对变体进行评估和分类。（1）根据已知，预测或可能的致病性对变体进行分类，并用解释性注释详细说明了其潜力或已知意义。

除非报道或预测引起疾病，否则内含子中发现的变化或不导致氨基酸取代的变化。

在GATA2gene may vary depending on the reference transcript used. When comparing the result to published literature this fact should be kept in mind.

临床相关性：

Some individuals who have involvement of one or more of the genes on the panel may have a variant that is not identified by the methods performed (eg, promoter variants, deep intronic variants). The absence of a variant, therefore, does not eliminate the possibility of disease. Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

对于无症状个体的预测测试，首先测试受影响的家庭成员通常很有用。在受影响的个体中鉴定致病变异可以对处于危险中的个体进行更多信息测试。

Technical Limitations:

Next-generation sequencing may not detect all types of genetic variants. Additionally, rare alterations (ie, polymorphisms) may be present that could lead to false-negative or false-positive results. If results do not match clinical findings, consider alternative methods for analyzing these genes, such as Sanger sequencing or large deletion/duplication analysis.

If the patient has had an allogeneic blood or bone marrow transplant or a recent (ie, <6 weeks from time of sample collection) heterologous blood transfusion, results may be inaccurate due to the presence of donor DNA.

Evaluation Tools:

可以使用多种计算机评估工具来帮助解释这些结果。在计算机评估工具中做出的预测的准确性高度取决于给定基因的数据，这些工具的预测可能会随着时间而变化。在计算机评估工具中的结果应谨慎解释和专业临床判断。

重新分类变体政策：

At this time, it is not standard practice for the laboratory to systematically review likely pathogenic variants or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time. Consultation with a healthcare provider, or team of healthcare providers, with expertise in genetics and primary immunodeficiencies, is recommended for interpretation of this result.

A list of benign and likely benign variants detected is available from the lab upon request.

如果需要有关用于分析结果的成绩单或人类基因组组装的其他信息，请与实验室联系。

1.Richards S，Aziz N，Bale S等人：序列变体解释的标准和准则：美国医学遗传学与基因组学学院的联合共识和分子病理协会。基因医学。2015年5月; 17（5）：405-424

2. Spinner MA, Sanchez LA, Hsu AP, et al: GATA2 deficiency: a protean disorder of hematopoiesis, lymphatics and immunity. Blood. 2014;123:809-821

3. Dickinson RE, Griffin H, Bigley V, et al: Exome sequencing identifies GATA-2 mutation as the cause of dendritic cells, monocyte, B and NK lymphoid deficiency. Blood. 2011;118:2656-2658

4. Hsu AP，Sampaio EP，Khan J等：突变GATA2与常染色体显性和零星单核细胞减少症和分枝杆菌感染（MONOMAC）综合征有关。血液。2011; 118：2653-2655

5. Mace EM, Hsu AP, Monaco-Shawver L, et al: Mutations inGATA2引起人类NK细胞缺乏，并具有CD56Bright子集的特异性损失。血液。2013; 121：2669-2677

6. Ostergaard P，Simpson MA，Connell FC等：突变GATA2cause primary lymphedema associated with a predisposition to acute myeloid leukemia (Emberger syndrome). Nat Genet. 2011;43:929-931. doi: 10.1038/ng.923

7. West RR, Hsu AP, Holland SM, Cuellar-Rodriguez J, Hickstein DD: Acquiredasxl1mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. Haematologica. 2014;99:276-281. doi: 10.3324/haematol.2013.090217

8. Cuellar-Rodriguez J，Gea-Banacloche J，Freeman AF等：成功的同种异体造血干细胞移植，用于GATA2缺乏。血液。2011; 118：3715-3720

9. Hsu AP, McReynolds LJ, Holland SM: GATA2 deficiency. Curr Opin Allergy Clin Immunol. 2015;15:104-109

• Informed Consent for Genetic Testing
• GATA2基因测序患者信息
• 基因检测的知情同意（西班牙）