[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT00001467":3,"trial-entities:NCT00001467":111,"trial-summary:NCT00001467":119},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":8,"brief_summary":14,"detailed_description":15,"conditions":16,"keywords":22,"study_type":28,"primary_purpose":8,"phases":29,"enrollment_info":30,"interventions":33,"primary_outcomes":34,"secondary_outcomes":42,"sex":54,"minimum_age":55,"maximum_age":56,"healthy_volunteers":57,"eligibility_criteria":58,"std_ages":62,"locations":66,"central_contacts":76,"overall_officials":86,"references":89,"see_also_links":107},"NCT00001467","950066","Genetic Analysis of Immune Disorders","RECRUITING",null,"2026-09-02","2026-09-16","1995-06-06","National Institute of Allergy and Infectious Diseases (NIAID)","NIH","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.\n\nPatients 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\u002F8 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.\n\nIf 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.\n\nInformation 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.","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.\n\nMembers 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.",[17,18,19,20,21],"DOK 8","STAT1","GATA2","Immunodeficiency","STAT3",[23,24,25,26,27],"Primary Immunodeficiency Disorders","Immunologic Disorders","Mutation","Genetic Analysis","Natural History","OBSERVATIONAL",[],{"count":31,"type":32},5000,"ESTIMATED",[],[35,39],{"measure":36,"description":37,"timeFrame":38},"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",{"measure":40,"description":41,"timeFrame":38},"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",[43,47,50],{"measure":44,"description":45,"timeFrame":46},"To track the natural history of disease outcome in selected disorders.","understanding of natural history of selected disorders","over time via history and assignment to other protocols",{"measure":48,"description":49,"timeFrame":38},"To perform genotype\u002Fphenotype 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",{"measure":51,"description":52,"timeFrame":53},"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\u002Fconditions of the immune system.caused by genetic mutations\u002Fdeficiencies","upon known or suspected diagnosis","ALL","1 Day","101 Years",false,{"inclusion":59,"exclusion":60,"raw_text":61},[],[],"* INCLUSION \u002F EXCLUSION CRITERIA:\n\nProbands 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.\n\nFetal samples may be studied in selected cases where benefit, such as expedited postnatal treatment, could be realized.",[63,64,65],"CHILD","ADULT","OLDER_ADULT",[67],{"facility":68,"status":7,"city":69,"state":70,"zip":71,"country":72,"geoPoint":73},"National Institutes of Health Clinical Center","Bethesda","Maryland","20892","United States",{"lat":74,"lon":75},38.98067,-77.10026,[77,82],{"name":78,"role":79,"phone":80,"email":81},"Steven M Holland, M.D.","CONTACT","(301) 402-7684","sholland@mail.nih.gov",{"name":83,"role":79,"phone":84,"email":85},"Gulbu Uzel, M.D.","(301) 451-9035","guzel@niaid.nih.gov",[87],{"name":83,"affiliation":12,"role":88},"PRINCIPAL_INVESTIGATOR",[90,94,97,100,104],{"pmid":91,"type":92,"citation":93},"8195317","BACKGROUND","Puck JM. Molecular and genetic basis of X-linked immunodeficiency disorders. J Clin Immunol. 1994 Mar;14(2):81-9. doi: 10.1007\u002FBF01541340.",{"pmid":95,"type":92,"citation":96},"7540117","Fisher 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\u002F0092-8674(95)90013-6.",{"pmid":98,"type":92,"citation":99},"7668284","Pepper 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":101,"type":102,"citation":103},"38194689","DERIVED","Donko 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\u002Fblood.2023022098.",{"pmid":105,"type":102,"citation":106},"24077845","West 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\u002Fhaematol.2013.090217. Epub 2013 Sep 27.",[108],{"label":109,"url":110},"NIH Clinical Center Detailed Web Page","https:\u002F\u002Fclinicalstudies.info.nih.gov\u002Fcgi\u002Fdetail.cgi?A_1995-I-0066.html",{"nct_id":4,"conditions":112,"biomarkers":114},[24,113],"Inborn Error of Immunity",[115,116,117,118],"DOCK8 Gene","GATA2 Gene","STAT1 Gene","STAT3 Gene",{"nct_id":4,"found":120,"summary":121,"prompt_version":130},true,{"design":122,"status":123,"heading":6,"summary":124,"follow_up":125,"word_count":126,"commitments":127,"compensation":128,"drugs_mentioned":129},"This is an observational study, meaning researchers will collect information without giving any specific treatments. It plans to include up to 5000 participants.","completed","This study aims to understand immune disorders, which are conditions where your body's defense system (immune system) doesn't work correctly. This can lead to problems fighting infections, allergies, or autoimmune diseases like lupus or arthritis. Researchers want to find the genes responsible for these disorders, learn about the health problems they cause, and predict who might develop them or pass them on to their children. You can join if you or a family member has an immune disorder that is thought to have a genetic cause. The study is looking for changes in genes like DOK8, STAT1, GATA2, and STAT3. Success will be measured by finding genetic changes and understanding how they affect the disorder. The current recruitment status is unclear, but the study plans to enroll up to 5000 people.","Not specified.",131,"You would provide blood samples for genetic testing. This testing would happen once or could be repeated.","Not stated in the trial record.",[],"v2"]