NCT03206099

Brief Summary

Background: Genetic testing called "sequencing" helps researchers look at DNA. Genes are made of DNA and are the instructions for our bodies to function. We all have thousands of genes. DNA variants are differences in genes between two people. We all have lots of variants. Most are harmless and some cause differences like blue or brown eyes. A few variants can cause health problems. Objective: To understand the genetics of immune disorders various health conditions, as well as outcomes of clinical genomics and genetic counseling services performed under this protocol. Eligibility: Participants in other NIH human subjects research protocols - either at the NIH Clinical Center (CC) or at Children s National Health System (CNHS) - (aged 0-99 years), and, in select cases, their biological relatives Design: Researchers will study participant s DNA extracted from blood, saliva, or another tissue sample, including previously collected samples we may have stored at the NIH. Researchers will look at participant s DNA in great detail. We are looking for differences in the DNA sequence or structure between participants and other people. Participants will receive results that:

  • Are important to their health
  • Have been confirmed in a clinical lab
  • Suggest that they could be at risk for serious disease that may affect your current or future medical management. Some genetic information we return to participants may be of uncertain importance. If genetic test results are unrelated to the participant s NIH evaluations, then we will not typically report:
  • Normal variants
  • Information about progressive, fatal conditions that have no effective treatment
  • Carrier status (conditions you don t have but could pass on) The samples and data will be saved for future research. Personal data will be kept as private as possible. If future studies need new information, participants may be contacted.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
20,000

participants targeted

Target at P75+ for all trials

Timeline
43mo left

Started Jul 2017

Longer than P75 for all trials

Geographic Reach
1 country

2 active sites

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

Study Progress71%
Jul 2017Dec 2029

First Submitted

Initial submission to the registry

June 30, 2017

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 2, 2017

Completed
29 days until next milestone

Study Start

First participant enrolled

July 31, 2017

Completed
12.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2029

Last Updated

June 5, 2026

Status Verified

April 14, 2026

Enrollment Period

12.4 years

First QC Date

June 30, 2017

Last Update Submit

June 4, 2026

Conditions

AutoimmunityAutoinflammationAtopyPrimary Immunodeficiency

Keywords

PhenotypingGeneticsSequencingInborn Errors of ImmunityGenomicsNatural History

Outcome Measures

Primary Outcomes (3)

  • Identifying novel genetic defects associated with immune disorders

    Identifying novel genetic defects associated with immune disorders

    Upon analysis of genomic data

  • Identifying novel clinical phenotypes associated with established genetic defects

    Identifying novel clinical phenotypes associated with established genetic defects

    Upon analysis of genomic data

  • Identifying established genetic disorders of the immune system

    Identifying established genetic disorders of the immune system, as well as known genetic disorders outside of the immune system in some cases

    Upon analysis of genomic data

Secondary Outcomes (1)

  • Evidence base for how to improve clinical genomic services on this protocol and related programs.

    5.1.1. Enrollment/Baseline Report Comprehension Survey and Semi-Structured Phone Interviews

Study Arms (3)

Biological relatives

Biological relatives of probands, who may or may not also be co-enrolled on the proband's referring protocol.

Healthy volunteers

Select internal controls

Probands

Participants with a disease under investigation by another NIAID protocol on which they are enrolled, either at the NIH or CNHS.

Eligibility Criteria

Age1 Day - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Probands and their biological relatives (primarily clinical), recruited from NIAID protocols (both at the NIH and CNHS).

You may qualify if:

  • Must fulfill one of the following criteria:
  • Proband participants: must be individuals under investigation by another NIH protocol on which they are co-enrolled, or are referred from the GDMCC protocol "Defining the Genetic Etiology of Suppurative Lung Disease in Children and Adults" (NCT04702243). Probands may have a disease under investigation or be healthy volunteers
  • Biological relatives: biologically related to a proband participant.
  • Aged 0-99 years.
  • Participants must be willing to undergo genetic testing.
  • Participants must be willing to allow samples to be stored for future research.
  • Participants must be willing to have their de-identified genomic data shared, for example in a controlled access databases like the Database of Genotypes and Phenotypes (dbGaP).
  • To complete surveys and interviews:
  • Proficient with the English language.
  • Able to provide informed consent.
  • Adult healthy volunteers must be able to provide informed consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

  • Zainab R, Kaur S, Lack J, Similuk M, Tandon M, Ghosh R, Seifert BA, Tokita M, Flippo C, Yan J, Walkiewicz M, Chittiboina P, Tatsi C. Genetic evaluation of pediatric pituitary adenomas and USP8-related genotype-phenotype correlations in Cushing's disease. Pituitary. 2025 Aug 14;28(5):92. doi: 10.1007/s11102-025-01557-6.

    PMID: 40813536DERIVED

  • Beers BJ, Similuk MN, Ghosh R, Seifert BA, Jamal L, Kamen M, Setzer MR, Jodarski C, Duncan R, Hunt D, Mixer M, Cao W, Bi W, Veltri D, Karlins E, Zhang L, Li Z, Oler AJ, Jevtich K, Yu Y, Hullfish H, Bielekova B, Frischmeyer-Guerrerio P, Dang Do A, Huryn LA, Olivier KN, Su HC, Lyons JJ, Zerbe CS, Rao VK, Keller MD, Freeman AF, Holland SM, Franco LM, Walkiewicz MA, Yan J. Chromosomal microarray analysis supplements exome sequencing to diagnose children with suspected inborn errors of immunity. Front Immunol. 2023 May 5;14:1172004. doi: 10.3389/fimmu.2023.1172004. eCollection 2023.

    PMID: 37215141DERIVED

  • Ferre EMN, Yu Y, Oikonomou V, Hilfanova A, Lee CR, Rosen LB, Burbelo PD, Vazquez SE, Anderson MS, Barocha A, Heller T, Soldatos A, Holland SM, Walkiewicz MA, Lionakis MS. Case report: Discovery of a de novo FAM111B pathogenic variant in a patient with an APECED-like clinical phenotype. Front Immunol. 2023 Feb 17;14:1133387. doi: 10.3389/fimmu.2023.1133387. eCollection 2023.

    PMID: 36875114DERIVED

  • Similuk MN, Yan J, Ghosh R, Oler AJ, Franco LM, Setzer MR, Kamen M, Jodarski C, DiMaggio T, Davis J, Gore R, Jamal L, Borges A, Gentile N, Niemela J, Lowe C, Jevtich K, Yu Y, Hullfish H, Hsu AP, Hong C, Littel P, Seifert BA, Milner J, Johnston JJ, Cheng X, Li Z, Veltri D, Huang K, Kaladi K, Barnett J, Zhang L, Vlasenko N, Fan Y, Karlins E, Ganakammal SR, Gilmore R, Tran E, Yun A, Mackey J, Yazhuk S, Lack J, Kuram V, Cao W, Huse S, Frank K, Fahle G, Rosenzweig S, Su Y, Hwang S, Bi W, Bennett J, Myles IA, De Ravin SS, Fuss I, Strober W, Bielekova B, Almeida de Jesus A, Goldbach-Mansky R, Williamson P, Kumar K, Dempsy C, Frischmeyer-Guerrerio P, Fisch R, Bolan H, Metcalfe DD, Komarow H, Carter M, Druey KM, Sereti I, Dropulic L, Klion AD, Khoury P, O' Connell EM, Holland-Thomas NC, Brown T, McDermott DH, Murphy PM, Bundy V, Keller MD, Peng C, Kim H, Norman S, Delmonte OM, Kang E, Su HC, Malech H, Freeman A, Zerbe C, Uzel G, Bergerson JRE, Rao VK, Olivier KN, Lyons JJ, Lisco A, Cohen JI, Lionakis MS, Biesecker LG, Xirasagar S, Notarangelo LD, Holland SM, Walkiewicz MA. Clinical exome sequencing of 1000 families with complex immune phenotypes: Toward comprehensive genomic evaluations. J Allergy Clin Immunol. 2022 Oct;150(4):947-954. doi: 10.1016/j.jaci.2022.06.009. Epub 2022 Jun 24.

    PMID: 35753512DERIVED

Related Links

MeSH Terms

Conditions

Primary Immunodeficiency DiseasesAutoimmune Diseases

Condition Hierarchy (Ancestors)

Genetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesImmunologic Deficiency SyndromesImmune System Diseases

Study Officials

  • Morgan N Similuk

    National Institute of Allergy and Infectious Diseases (NIAID)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Morgan N Similuk

CONTACT

(301) 435-6691morgan.similuk@nih.gov

Study Design

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

Study Record Dates

First Submitted

June 30, 2017

First Posted

July 2, 2017

Study Start

July 31, 2017

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2029

Last Updated

June 5, 2026

Record last verified: 2026-04-14

Locations

US(2)