Natural History Study of GATA2 Deficiency and Related Disorders

Background: \- GATA2 deficiency is a genetic disorder that can cause problems with a person s immune system and other body systems. Some people who have this disorder develop few problems from it. Others can have a wide range of health problems, from skin problems, to hearing loss, to cancer. These problems can happen at any age. Researchers want to study GATA2 deficiency to better understand what types of health problems it can cause, and why it causes problems in some people but not others, and at different ages. Objectives: \- To improve understanding of GATA2 deficiency so there can be better diagnostic tests and treatments in the future. Eligibility: \- People 2 years of age or older who have a GATA2 gene mutation or certain health conditions that are commonly seen in people with this mutation and their blood relatives. Design: * Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected to see whether participants have the GATA2 genetic mutation. Several other tests may be recommended, but participants can decline to take them. * Participants will be eligible to receive standard care for GATA2 deficiency through this protocol. They may be eligible for other clinical trials at the National Institutes of Health as well. * Participants will have regular study visits once a year to evaluate their GATA2 deficiency. Participants will take part in the study for at least 3 years and up to 15 years. At these follow-up visits, participants will fill out a questionnaire and take a physical exam and blood tests. Other tests may be performed as needed.

Sex

All

Minimum age

2 Years

Maximum age

100 Years

* INCLUSION CRITERIA:

Males and females greater than or equal to 2 years old must meet the following criteria to be eligible for participation in this study:

* Have a mutation in GATA2 proven by genetic testing (previous test results will be accepted) OR meet both of the following criteria:

  * Clinical characteristics strongly consistent with GATA2 deficiency per the following criteria and at the discretion of the principal investigator (PI). Individuals without a GATA2 mutation must have a past or present history of 1 or more of the following to be considered for study enrollment:

    * Disseminated NTM or invasive fungal infection.
    * Severe or recurrent HPV or herpesvirus infection.
    * MDS, AML, or CMML.
    * Biopsy-proven PAP.
  * Laboratory characteristics strongly consistent with GATA2 deficiency per the following criteria. Individuals without a GATA2 mutation must have 1 or more of the following to be considered for study enrollment:

    * Absolute monocyte count \<240 cells/microL.
    * Absolute B lymphocyte count \<60 cells/microL.
    * Absolute NK lymphocyte count \<126 cells/microL.
* Agree to undergo genetic testing.
* Allow their samples to be stored for future research.

RELATIVE INCLUSION CRITERIA:

Blood relatives, male or female, greater than or equal to 2 years old, of any patient on this study. If a relative is positive for GATA2 then they could become a patient on the study.

SUBJECT EXCLUSION CRITERIA:

Individuals with any condition or who are taking any medications that, in the opinion of the investigator, contraindicates participation in the study will be excluded.

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• BACKGROUNDBigley V, Haniffa M, Doulatov S, Wang XN, Dickinson R, McGovern N, Jardine L, Pagan S, Dimmick I, Chua I, Wallis J, Lordan J, Morgan C, Kumararatne DS, Doffinger R, van der Burg M, van Dongen J, Cant A, Dick JE, Hambleton S, Collin M. The human syndrome of dendritic cell, monocyte, B and NK lymphoid deficiency. J Exp Med. 2011 Feb 14;208(2):227-34. doi: 10.1084/jem.20101459. Epub 2011 Jan 17. PMID 21242295
• BACKGROUNDHsu AP, Sampaio EP, Khan J, Calvo KR, Lemieux JE, Patel SY, Frucht DM, Vinh DC, Auth RD, Freeman AF, Olivier KN, Uzel G, Zerbe CS, Spalding C, Pittaluga S, Raffeld M, Kuhns DB, Ding L, Paulson ML, Marciano BE, Gea-Banacloche JC, Orange JS, Cuellar-Rodriguez J, Hickstein DD, Holland SM. Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood. 2011 Sep 8;118(10):2653-5. doi: 10.1182/blood-2011-05-356352. Epub 2011 Jun 13. PMID 21670465
• DERIVEDWest RR, Bauer TR, Tuschong LM, Embree LJ, Calvo KR, Tillo D, Davis J, Holland SM, Hickstein DD. A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins. Blood Adv. 2023 Oct 24;7(20):6351-6363. doi: 10.1182/bloodadvances.2023010458. PMID 37595058
• DERIVEDWu Z, Gao S, Diamond C, Kajigaya S, Chen J, Shi R, Palmer C, Hsu AP, Calvo KR, Hickstein DD, Holland SM, Young NS. Sequencing of RNA in single cells reveals a distinct transcriptome signature of hematopoiesis in GATA2 deficiency. Blood Adv. 2020 Jun 23;4(12):2656-2670. doi: 10.1182/bloodadvances.2019001352.