Genetic Analysis of Immune Disorders
2 other identifiers
observational
5,000
1 country
1
Brief Summary
The purposes of this study are to 1) identify the genes responsible for certain immune disorders, 2) learn about the medical problems they cause, and 3) learn how to predict who is likely to develop these disorders and what the risk is of passing them on to children. The immune system is the body s defense system. Some immune deficiencies impair a person s ability to fight infections; others render a person susceptible to allergies, or to autoimmune diseases such as lupus or arthritis, in which the immune cells (white blood cells) attack and destroy the body s own tissues. Patients with immune disorders known or suspected to have a genetic basis and their family members may enroll in this study. Eligibility will be determined by a review of the patient s medical records and family medical history. Participants will provide a small blood sample for genetic (DNA) and white blood cell analysis. Gene samples (but not white blood cells) may also be obtained by mouth brushing or skin biopsy. For the mouth brushing, a small brush is rubbed against the inside of the cheeks for 1 minute to wipe off some cells. For the skin biopsy, a small circle of skin (about 1/8 inch) is removed under local anesthetic. Pregnant women may be asked to provide a fetal sample (amniotic fluid cells or chorionic villus sample). All samples will be used for immune or genetic studies of the family s immune disorder. If test results show a specific genetic variation responsible for the family s immune disorder, a report will be sent to the patient s doctor or genetic counselor, who will discuss the implications for the family. NIH researchers and genetic counselors will also be available to explain results and answer questions. Information will not be available in the case of disorders that cannot yet be linked to a specific genetic abnormality. Information from this study will increase knowledge about the immune system and what causes immune deficiencies. Participants may also learn the underlying cause of an immune disorder that affects them or someone in their family information may be useful in guiding treatment and in making decisions regarding family planning.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
1 active site
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 Start
First participant enrolled
June 6, 1995
CompletedFirst Submitted
Initial submission to the registry
November 3, 1999
CompletedFirst Posted
Study publicly available on registry
November 4, 1999
CompletedMay 7, 2026
August 21, 2025
November 3, 1999
May 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To search for modifiers of phenotype in subjects with disorders of the immune system in which penetrance and expressivity are variable.
Greater understanding of the variable penetrance and expressivity of modifiers of phenotype in subjects with disorders of the immune system
blood draw and testing once or can be repeated
genetic testing for known or suspected mutations related to primary immune deficiencies
diagnosis of genetic mutations or deficiencies causing rare primary immune diseases under study
blood draw and testing once or can be repeated
Secondary Outcomes (3)
To track the natural history of disease outcome in selected disorders.
over time via history and assignment to other protocols
To perform genotype/phenotype analysis in subjects with immune defects of known genetic cause, leading to basic research on interactions between components of receptors in immune system pathways.
blood draw and testing once or can be repeated
To identify by clinical and laboratory studies, including mutation detection in patients and healthy relatives who may be carriers, subjects who may be eligible for related protocols or who may derive clinical benefit from molecular diagnosis.
upon known or suspected diagnosis
Study Arms (2)
Blood relatives
blood related family members of proband
Proband
person initially ill/studied/diagnosed
Eligibility Criteria
Probands and their blood relatives, of any age, sex, and ethnicity, who are affected, or suspected of being affected with genetic conditions and immune dysregulations under study are eligible to enroll as patients or family member enrollees. Fetal samples may be studied in selected cases where benefit, such as expedited postnatal treatment, could be realized.
You may not qualify if:
- Probands and their blood relatives, of any age, and ethnicity, who are affected, or suspected of being affected with genetic conditions and immune dysregulations under study are eligible to enroll as patients and family member enrollees.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Publications (5)
Puck JM. Molecular and genetic basis of X-linked immunodeficiency disorders. J Clin Immunol. 1994 Mar;14(2):81-9. doi: 10.1007/BF01541340.
PMID: 8195317BACKGROUNDFisher GH, Rosenberg FJ, Straus SE, Dale JK, Middleton LA, Lin AY, Strober W, Lenardo MJ, Puck JM. Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell. 1995 Jun 16;81(6):935-46. doi: 10.1016/0092-8674(95)90013-6.
PMID: 7540117BACKGROUNDPepper AE, Buckley RH, Small TN, Puck JM. Two mutational hotspots in the interleukin-2 receptor gamma chain gene causing human X-linked severe combined immunodeficiency. Am J Hum Genet. 1995 Sep;57(3):564-71.
PMID: 7668284BACKGROUNDDonko A, Sharapova SO, Kabat J, Ganesan S, Hauck FH, Bergerson JRE, Marois L, Abbott J, Moshous D, Williams KW, Campbell N, Martin PL, Lagresle-Peyrou C, Trojan T, Kuzmenko NB, Deordieva EA, Raykina EV, Abers MS, Abolhassani H, Barlogis V, Milla C, Hall G, Mousallem T, Church J, Kapoor N, Cros G, Chapdelaine H, Franco-Jarava C, Lopez-Lerma I, Miano M, Leiding JW, Klein C, Stasia MJ, Fischer A, Hsiao KC, Martelius T, Seppanen MRJ, Barmettler S, Walter J, Masmas TN, Mukhina AA, Falcone EL, Kracker S, Shcherbina A, Holland SM, Leto TL, Hsu AP. Clinical and functional spectrum of RAC2-related immunodeficiency. Blood. 2024 Apr 11;143(15):1476-1487. doi: 10.1182/blood.2023022098. Erratum In: Blood. 2024 Sep 5;144(10):1132. doi: 10.1182/blood.2024025827.
PMID: 38194689DERIVEDWest RR, Hsu AP, Holland SM, Cuellar-Rodriguez J, Hickstein DD. Acquired ASXL1 mutations are common in patients with inherited GATA2 mutations and correlate with myeloid transformation. Haematologica. 2014 Feb;99(2):276-81. doi: 10.3324/haematol.2013.090217. Epub 2013 Sep 27.
PMID: 24077845DERIVED
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Gulbu Uzel, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- OTHER
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 3, 1999
First Posted
November 4, 1999
Study Start
June 6, 1995
Last Updated
May 7, 2026
Record last verified: 2025-08-21
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- ICF
- Time Frame
- PD and supporting information will be available after completion of the study.
- Access Criteria
- Data will be shared through:@@@@@@-Approved outside collaborators under appropriate individual agreements.@@@@@@-Publication and/or public presentations.@@@@@@Data might be shared before publication.@@@@@@The PI will review all requests for sharing data.
We will share human data generated in this study for future research as follows:@@@@@@-Identified data in the Biomedical Translational Research Information System (BTRIS, automatic for activities in the NIH CC).@@@@@@-De-identified or identified data with approved outside collaborators under appropriate agreements.@@@@@@-Data sharing may be complicated or limited in certain cases by contractual obligations or agreements with outside collaborators, such as cooperative research and development agreements, clinical trial agreements, other restraints, etc.