Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders

NCT07683104 | Recruiting

• 2 other identifiers: 10002326002326-I
• Study Type: observational
• Target: 750
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Trisomy 8 mosaicism is a genetic disorder that can increase inflammation in the body. Symptoms include fevers; sores or ulcers in the mouth, digestive tract, or genital area; skin rashes; problems in organs or tissues; and changes in bone marrow cells. Researchers want to conduct a natural history study to learn more about these symptoms and what causes them. Objective: To gather data and samples from people with and without the trisomy 8 mosaicism. Eligibility: People of any age with the trisomy 8 gene mosaicism. Their healthy relatives are also needed. Design: Affected participants will have visits every 1 to 2 years for 30 years at NIH. Each visit will take 1 to 5 days and may be in-person or remote. With remote visits, participants may have a video call with the study team and samples may be sent to researchers by mail. Participants may have these procedures: Physical exam, with blood tests. Tests of brain function and motor skills. Sensory tests. Researchers will see how participants respond to sensations such as pinpricks, heat, cold, and pressure. Magnetic resonance imaging (MRI) scan of the brain and/or spine. X-ray of the spine. Ultrasound test of heart function (echocardiogram). Tissues samples (biopsies) collected from the skin, inside of the mouth, and bone marrow. Swabs to collect cells from the mouth, skin, and vagina. Collection of blood, stool, urine, saliva, hair, and fingernail samples. X-rays, MRI, and heart tests will be done only once. Other procedures may be repeated at each visit. All tests and procedures are voluntary. Healthy relatives who enroll will have a baseline visit and then follow-up visits as needed. They will have a physical exam. The inside of their mouth may be swabbed. Samples of blood, stool, urine, and saliva may be taken.

Conditions

Mucosal Ulcerations; Trisomy 8 Associated Autoinflammatory Disease; Trisomy 8 Mosaicism

Keywords

Genital Ulcers; Myelodysplastic Syndromes; Mucosal ulcerations; Recurrent fever; Oral aphthous ulcers; Autoinflammatory disease; Trisomy 8 mosaicism

Outcome Measures

Primary Outcomes (2)

• Clinical characterization of participants with trisomy 8 mosaicism and related disorders based on history, physical examination, radiologic imaging, and laboratory testing.

  Characterize the clinical spectrum and natural history of trisomy 8 mosaicism and related disorders.

  Length of the study

• Characterization of immunologic profile of participants with trisomy 8 mosaicism and related disorders over time in comparison to healthy controls using cellular and molecular techniques

  Characterization of immunologic profile of participants with trisomy 8 mosaicism and related disorders over time in comparison to healthy controls using cellular and molecular techniques including, but not limited to immune cell phenotyping, transcriptomics, proteomics, and ex vivo functional studies.

  Length of the study

Secondary Outcomes (4)

• Characterization of laboratory, radiologic examinations, biopsies, and physical exam findings.

  Length of study

• Identification of individuals with trisomy 8 who develop malignancy and assessment of risk factors including but not limited to history, findings on bone marrow biopsies and CBCs, NGS for risk variants, and flow cytometry.

  Length of study

• Determination of the percentage of trisomy 8 cells in various tissue types including bone marrow, blood, fibroblasts cultured from skin, and biopsy samples, and the association with clinical phenotype.

  Length of study

• Assessment of treatment response based on inflammatory markers, clinical history, and physical exam findings.

  Length of study

Study Arms (2)

Affected Participants

Individuals ages \<= 99 with known or suspected trisomy 8 mosaicism, or with clinical phenotype consisting of mucosal ulcerations similar to TRIAD.

Non-affected biological family member participants

Non-affected biological family members of enrolled participants.

Eligibility Criteria

• Age: 1 Day - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Outside provider referral, current NIH study patients

You may qualify if:

• To be eligible to participate in this study, an individual must meet the following criteria:
• Stated willingness to comply with study requirements.
• Aged \<= 99 (ability to be seen at NIH vs. remote visit may be determined by age and location).
• Willingness to allow storage of data and specimens for future research.
• Must have one of the following:
• Trisomy 8 mosaicism verified by genetic testing (including but not limited to karyotype, fluorescence in situ hybridization \[FISH\], whole genome sequencing \[WGS\], whole exome sequencing \[WES\], or microarray), or
• Inflammatory mucosal ulcerative disease clinically similar to TRIAD at the discretion of the principal investigator.
• Ability of participant or LAR to provide informed consent.
• Be an unaffected biological relative of an affected participant.
• Ability to provide informed consent.
• Willingness to provide at least one biospecimen.

You may not qualify if:

• Individuals with any condition or who are taking any medications that, in the opinion of the investigator, contraindicates participation in the study will be excluded.
• Co-enrollment guidelines: Enrollment in this protocol does not preclude individuals from enrolling or participating in any other NIH protocols, including studies of investigational agents. Participants will be asked about their participation in other studies to ensure that blood draws do not exceed NIH limits for research protocols.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (14)

• Ando S, Maemori M, Sakai H, Ando S, Shiraishi H, Sakai K, Ruhnke GW. Constitutional trisomy 8 mosaicism with myelodysplastic syndrome complicated by intestinal Behcet disease and antithrombin III deficiency. Cancer Genet Cytogenet. 2005 Oct 15;162(2):172-5. doi: 10.1016/j.cancergencyto.2005.01.010.

  PMID: 16213367 BACKGROUND

• Becker K, Fitzgerald O, Green AJ, Keogan M, Newbury-Ecob R, Greenhalgh L, Withers S, Hollox EJ, Aldred PM, Armour JA. Constitutional trisomy 8 and Behcet syndrome. Am J Med Genet A. 2009 May;149A(5):982-6. doi: 10.1002/ajmg.a.32756.

  PMID: 19353586 BACKGROUND

• Hasle H, Clausen N, Pedersen B, Bendix-Hansen K. Myelodysplastic syndrome in a child with constitutional trisomy 8 mosaicism and normal phenotype. Cancer Genet Cytogenet. 1995 Jan;79(1):79-81. doi: 10.1016/0165-4608(94)00099-w.

  PMID: 7850757 BACKGROUND

• Altiner S, Kutlay NY, Ilhan O. Constitutional Trisomy 8 Mosaicism with Persistent Macrocytosis. Cytogenet Genome Res. 2016;150(1):35-39. doi: 10.1159/000452358. Epub 2016 Nov 12.

  PMID: 27838684 BACKGROUND

• Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results from a 13-year incidence study in Arhus, Denmark. Hum Genet. 1991 May;87(1):81-3. doi: 10.1007/BF01213097.

  PMID: 2037286 BACKGROUND

• Saumell S, Sole F, Arenillas L, Montoro J, Valcarcel D, Pedro C, Sanzo C, Luno E, Gimenez T, Arnan M, Pomares H, De Paz R, Arrizabalaga B, Jerez A, Martinez AB, Sanchez-Castro J, Rodriguez-Gambarte JD, Raya JM, Rios E, Rodriguez-Rivera M, Espinet B, Florensa L. Trisomy 8, a Cytogenetic Abnormality in Myelodysplastic Syndromes, Is Constitutional or Not? PLoS One. 2015 Jun 12;10(6):e0129375. doi: 10.1371/journal.pone.0129375. eCollection 2015.

  PMID: 26066831 BACKGROUND

• Maserati E, Aprili F, Vinante F, Locatelli F, Amendola G, Zatterale A, Milone G, Minelli A, Bernardi F, Lo Curto F, Pasquali F. Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases. Genes Chromosomes Cancer. 2002 Jan;33(1):93-7. doi: 10.1002/gcc.1214.

  PMID: 11746991 BACKGROUND

• Baidas S, Chen TJ, Kolev V, Wong LJ, Imholte J, Qin N, Meck J. Constitutional trisomy 8 mosaicism due to meiosis II non-disjunction in a phenotypically normal woman with hematologic abnormalities. Am J Med Genet A. 2004 Feb 1;124A(4):383-7. doi: 10.1002/ajmg.a.20390.

  PMID: 14735586 BACKGROUND

• Seghezzi L, Maserati E, Minelli A, Dellavecchia C, Addis P, Locatelli F, Angioni A, Balloni P, Miano C, Cavalli P, Danesino C, Pasquali F. Constitutional trisomy 8 as first mutation in multistep carcinogenesis: clinical, cytogenetic, and molecular data on three cases. Genes Chromosomes Cancer. 1996 Oct;17(2):94-101. doi: 10.1002/(SICI)1098-2264(199610)17:23.0.CO;2-W.

  PMID: 8913726 BACKGROUND

• Manthiram K, Preite S, Dedeoglu F, Demir S, Ozen S, Edwards KM, Lapidus S, Katz AE; Genomic Ascertainment Cohort; Feder HM Jr, Lawton M, Licameli GR, Wright PF, Le J, Barron KS, Ombrello AK, Barham B, Romeo T, Jones A, Srinivasalu H, Mudd PA, DeBiasi RL, Gul A, Marshall GS, Jones OY, Chandrasekharappa SC, Stepanovskiy Y, Ferguson PJ, Schwartzberg PL, Remmers EF, Kastner DL. Common genetic susceptibility loci link PFAPA syndrome, Behcet's disease, and recurrent aphthous stomatitis. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14405-14411. doi: 10.1073/pnas.2002051117. Epub 2020 Jun 9.

  PMID: 32518111 BACKGROUND

• Wesner N, Drevon L, Guedon A, Fraison JB, Trad S, Kahn JE, Aouba A, Gillard J, Ponsoye M, Hanslik T, Gourguechon C, Liozon E, Laribi K, Rossignol J, Hermine O, Ades L, Carrat F, Fenaux P, Mekinian A, Fain O; GFM, MINHEMON (French Network of Dysimmune Disorders Associated to Hemopathies). Inflammatory disorders associated with trisomy 8-myelodysplastic syndromes: French retrospective case-control study. Eur J Haematol. 2019 Jan;102(1):63-69. doi: 10.1111/ejh.13174. Epub 2018 Nov 14.

  PMID: 30218579 BACKGROUND

• Wesner N, Drevon L, Guedon A, Fraison JB, Terrier B, Trad S, Kahn JE, Aouba A, Gillard J, Ponsoye M, Hanslik T, Gourguechon C, Liozon E, Laribi K, Rossignol J, Hermine O, Seksik P, Ades L, Carrat F, Fenaux P, Mekinian A, Fain O; On behalf GFM and MINHEMON (French Network of dysimmune disorders associated with hemopathies). Gastrointestinal Behcet's-like disease with myelodysplastic neoplasms with trisomy 8: a French case series and literature review. Leuk Lymphoma. 2019 Jul;60(7):1782-1788. doi: 10.1080/10428194.2018.1542152. Epub 2018 Nov 20.

  PMID: 30457024 BACKGROUND

• Ades L, Itzykson R, Fenaux P. Myelodysplastic syndromes. Lancet. 2014 Jun 28;383(9936):2239-52. doi: 10.1016/S0140-6736(13)61901-7. Epub 2014 Mar 21.

  PMID: 24656536 BACKGROUND

• Garcia-Manero G, Chien KS, Montalban-Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020 Nov;95(11):1399-1420. doi: 10.1002/ajh.25950.

  PMID: 32744763 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Chromosome 8, mosaic trisomy; Myelodysplastic Syndromes; Relapsing Fever; Foot-and-Mouth Disease

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Borrelia Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Tick-Borne Diseases; Vector Borne Diseases; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Animal Diseases

Study Officials

• Kalpana Manthiram, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura E Failla, C.R.N.P.

CONTACT

(240) 669-5323; laura.failla@nih.gov

Kalpana Manthiram, M.D.

CONTACT

(301) 529-4787; kalpana.manthiram@nih.gov

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2026
• First Posted: July 6, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): May 1, 2056
• Study Completion (Estimated): June 1, 2056
• Last Updated: July 31, 2026

Record last verified: 2026-07-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, CSR, ANALYTIC CODE
• Time Frame: Upon publication
• Access Criteria: Requests will be assessed by the PI. Next generation sequencing data will be deposited into public repositories.

Locations

US (1)