NCT01905826

Brief Summary

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
600

participants targeted

Target at P75+ for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 18, 2013

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 23, 2013

Completed
1 month until next milestone

Study Start

First participant enrolled

August 26, 2013

Completed
14.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2028

Expected
Last Updated

April 30, 2026

Status Verified

April 22, 2026

Enrollment Period

14.6 years

First QC Date

July 18, 2013

Last Update Submit

April 29, 2026

Conditions

GATA2 Deficiency

Keywords

Myelodysplastic SyndromesHerpesvirusDisseminated nontuberculous Mycobacterial (NTM)human papillomavirus (HPV)LeukemiaNatural History

Outcome Measures

Primary Outcomes (1)

  • Prospectively follow patients with GATA2 deficiency or phenotypic characteristics strongly consistent with GATA2 deficiency to characterize the full spectrum of clinical disease, better understand the reasons for phenotypic variability, better u...

    Collecting information on GATA2 deficiency.

    ongoing

Study Arms (2)

Patient Relatives

Blood relatives of enrolled patients.

Patients

Patients with known mutations in GATA2 or those with clinical and laboratory characteristics strongly consistent with GATA2 deficiency.

Eligibility Criteria

Age2 Years - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients \>=2 years old with known mutations in GATA2 or those with clinical and laboratory characteristics strongly consistent with GATA2 deficiency will be enrolled along with any of their blood relatives.

You may qualify if:

  • 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.
  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (5)

  • Vinh DC, Patel SY, Uzel G, Anderson VL, Freeman AF, Olivier KN, Spalding C, Hughes S, Pittaluga S, Raffeld M, Sorbara LR, Elloumi HZ, Kuhns DB, Turner ML, Cowen EW, Fink D, Long-Priel D, Hsu AP, Ding L, Paulson ML, Whitney AR, Sampaio EP, Frucht DM, DeLeo FR, Holland SM. Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia. Blood. 2010 Feb 25;115(8):1519-29. doi: 10.1182/blood-2009-03-208629. Epub 2009 Dec 29.

    PMID: 20040766BACKGROUND

  • Bigley 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: 21242295BACKGROUND

  • Hsu 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: 21670465BACKGROUND

  • West 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: 37595058DERIVED

  • Wu 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.

    PMID: 32556286DERIVED

Related Links

MeSH Terms

Conditions

GATA2 DeficiencyMyelodysplastic SyndromesHerpes SimplexLeukemia

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsSkin Diseases, ViralSkin Diseases, InfectiousSkin DiseasesSkin and Connective Tissue DiseasesNeoplasms by Histologic TypeNeoplasms

Study Officials

  • Steven M Holland, M.D.

    National Institute of Allergy and Infectious Diseases (NIAID)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Audrey M Neale

CONTACT

(240) 506-4024audrey.neale@nih.gov

Steven M Holland, M.D.

CONTACT

(301) 402-7684sholland@mail.nih.gov

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 18, 2013

First Posted

July 23, 2013

Study Start

August 26, 2013

Primary Completion (Estimated)

March 31, 2028

Last Updated

April 30, 2026

Record last verified: 2026-04-22

Data Sharing

IPD Sharing
Will share

Relevant individual participant data collected during the trial, after deidentification.

Shared Documents
SAP
Time Frame
Available on reasonable request after completion of the trial. No end date.
Access Criteria
It will be shared with researchers wishing to access the date for research project. To gain access, data requestors will need to sign Data Access/Use Agreement and provide supporting documentation.

Locations

US(1)