DOK 8NCT00001467
Genetic Analysis of Immune Disorders
An observational study of DOK 8 and STAT1, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 101 years
- How many people
- 5,000 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jun 1995to not given
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 101 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: 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.
Who may be able to join
- Probands and their blood relatives, of any age, gender, 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.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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....
Read the detailed description
This protocol includes studies of genetic defects of the immune system that cause failure of host defenses against infections, immune dysregulation, and autoimmune diseases. Numerous rare disorders result from inherited or newly arising mutations in genes involved in the development and function of innate and adaptive immune systems or both. As specific disease syndromes are defined and the responsible genes identified, mutations in individual families can be sought. Correlation of mutation sites with clinical information helps to determine how specific gene segments encode important functional domains of the proteins of the immune system within the same genetic defect. Rare, single gene disorders identify immunologic pathways that might contribute to more common conditions, such as failure to respond to vaccines, susceptibility to allergies, or autoimmune diseases like arthritis or lupus.
Members of families with immune disorders that are known or suspected to have a genetic basis may be eligible. Immunologic tests and DNA sequence analysis appropriate to each clinical condition will be performed as needed on affected individuals and at-risk family members. Healthy family members may serve as controls. Probands, parents of deceased affected individuals, or entire families, may be referred to the Investigators Initially, clinical and family history as well as laboratory data will be reviewed by the investigators to determine eligibility. Subjects considered appropriate will be invited through their referring physician to participate by signing our consent form and sending appropriate blood, DNA or other samples to our PI. Should a genetic basis for an individual s immune disorder be identified or if clinical eligibility for other protocols is met, they may be invited to visit NIH.
- Conditions
- DOK 8, STAT1, GATA2, Immunodeficiency, STAT3
- Keywords
- Primary Immunodeficiency Disorders, Immunologic Disorders, Mutation, Genetic Analysis, Natural History
- Medical subject headings
- Immunologic Deficiency Syndromes, Primary Immunodeficiency Diseases, Immune System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Blood relatives | blood related family members of proband | |
| Proband | person initially ill/studied/diagnosed |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: blood draw and testing once or can be repeated
Secondary outcomes (3)
To track the natural history of disease outcome in selected disorders.
understanding of natural history of selected disorders
Measured: 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.
understanding of interactions between components of receptors in immune system pathways in immune defects of know genetic cause
Measured: 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.
To follow patients and relatives that are affected or carriers of genetic defects over time and gain of further understanding of the natural history of diseases/conditions of the immune system.caused by genetic mutations/deficiencies
Measured: upon known or suspected diagnosis
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start6 Jun 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for DOK 8Studies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Gulbu Uzel, M.D., Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001467
- Sponsor's protocol ID
- 950066
- Other IDs
- 95-I-0066
- Status last verified
- 17 Sep 2026
- First submitted
- 3 Nov 1999
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Puck JM. Molecular and genetic basis of X-linked immunodeficiency disorders. J Clin Immunol. 1994 Mar;14(2):81-9. doi: 10.1007/BF01541340.
PubMed 8195317Fisher 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.
PubMed 7540117Pepper 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.
PubMed 7668284Donko 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.
PubMed 38194689West 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.
PubMed 24077845