Analiza genetyczna zaburzeń immunologicznych
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.
Przegląd badań
Status
Szczegółowy opis
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.
Typ studiów
Zapisy (Szacowany)
Kontakty i lokalizacje
Kontakt w sprawie studiów
- Nazwa: Gulbu Uzel, M.D.
- Numer telefonu: (301) 451-9035
- E-mail: guzel@niaid.nih.gov
Kopia zapasowa kontaktu do badania
- Nazwa: Steven M Holland, M.D.
- Numer telefonu: (301) 402-7684
- E-mail: sholland@mail.nih.gov
Lokalizacje studiów
-
-
Maryland
-
Bethesda, Maryland, Stany Zjednoczone, 20892
- Rekrutacyjny
- National Institutes of Health Clinical Center
-
-
Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Metoda próbkowania
Badana populacja
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.
Opis
- INCLUSION / EXCLUSION CRITERIA:
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.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Modele obserwacyjne: OTHER
- Perspektywy czasowe: CROSS_SECTIONAL
Kohorty i interwencje
Grupa / Kohorta |
|---|
|
Blood relatives
blood related family members of proband |
|
Proband
person initially ill/studied/diagnosed |
Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
To search for modifiers of phenotype in subjects with disorders of the immune system in which penetrance and expressivity are variable.
Ramy czasowe: blood draw and testing once or can be repeated
|
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
Ramy czasowe: blood draw and testing once or can be repeated
|
diagnosis of genetic mutations or deficiencies causing rare primary immune diseases under study |
blood draw and testing once or can be repeated
|
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
To track the natural history of disease outcome in selected disorders.
Ramy czasowe: over time via history and assignment to other protocols
|
understanding of natural history of 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.
Ramy czasowe: blood draw and testing once or can be repeated
|
understanding of interactions between components of receptors in immune system pathways in immune defects of know genetic cause |
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.
Ramy czasowe: upon known or suspected 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 |
upon known or suspected diagnosis
|
Współpracownicy i badacze
Śledczy
- Główny śledczy: Gulbu Uzel, M.D., National Institute of Allergy and Infectious Diseases (NIAID)
Publikacje i pomocne linki
Publikacje ogólne
- 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/haematol.2013.090217. Epub 2013 Sep 27.
- Puck JM. Molecular and genetic basis of X-linked immunodeficiency disorders. J Clin Immunol. 1994 Mar;14(2):81-9. doi: 10.1007/BF01541340.
- 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: 10.1016/0092-8674(95)90013-6.
- 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.
- 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/blood.2023022098.
Przydatne linki
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Szacowany)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
- 950066
- 95-I-0066
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
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.
Ramy czasowe udostępniania IPD
PD and supporting information will be available after completion of the study.
Kryteria dostępu do udostępniania IPD
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.
Typ informacji pomocniczych dotyczących udostępniania IPD
- ICF
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .