Genetic Analysis of Uncommon Disease Presentations in Non-US Populations

NCT06595940 | Recruiting

• 2 other identifiers: 10001645001645-HG
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Genetics research over the past 20 years has helped researchers find the causes of many diseases. More powerful tools for genetic testing now exist. Researchers want to use these new tools to learn more about genetic diseases. They want to look for possible genetic causes of unusual diseases. They will focus on people who live outside of the United States and whose access to genetic testing has been limited. Objective: To look for potential genetic sources of diseases among children and their families. Eligibility: Children aged 2 to 18 years and their related family members who have or may have a genetic disease. They will reside primarily outside of the US. Design: Participants will be recruited at sites outside of the US. Participants will be screened. Their existing medical records will be reviewed. They will have a physical exam. They will answer questions about their family history and symptoms. Participants will provide samples for genetic testing. They may have blood drawn. They may spit saliva into a small container. They may have a cotton swab rubbed on the inside of the mouth. The samples will be shipped to the NIH for genetic testing. Participants will be notified if testing reveals a known disease. Participants may be asked to provide new samples to confirm the diagnosis. Local study teams will contact the participants about the results. Participants will also be notified if analysis yields gene variants that may cause disease.

Conditions

Undiagnosed Diseases; Rare Diseases

Keywords

Genetics; Genomic sequencing; Under-represented populations; Medical genetics; Clinical Phenotype; Uncommon disease

Outcome Measures

Primary Outcomes (1)

• Exhaustion of available genomic interrogation techniques to determine the etiology of unconventional clinical phenotypes.

  The outcome will be achieved when we have reached a point where use of appropriate genomic interrogation techniques does not yield new pathophysiological insights.

  10 years

Secondary Outcomes (1)

• Independence and autonomy when conducting genetic studies among sites with limited to no access to medical genetics.

  10 years

Study Arms (2)

Affected

Individuals with a condition that is expected to be caused by a genetic change

Unaffected

Individuals who are first-degree relatives (parents, siblings, children) of affected individuals enrolled in this study

Eligibility Criteria

• Age: 2 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

To be eligible to participate in this study, an individual must meet all of the following criteria: willingness to comply with all study procedures and availability for the duration of the study; age \>2 years when enrolled in the study; suspicion of genetic cause for illness due to strong family history, young age of onset, illness being either more or less severe than expected; verification of meeting clinical inclusion criteria by reviewing a participant's medical record; ability of participant and their parent or guardian (if \<18 years old) to understand and willingly sign informed consent document. Those with previous genetic testing that was positive, those with evidence that their symptoms are caused by a condition unlikely to be genetic, or those with conditions that may interfere with their ability to participate in required testing will be excluded from this study.

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Probands aged \>2 years at enrollment or first-degree relatives of probands (age \>2 years).
• Suspicion of genetic etiology of illness due to strong family history, precocious onset, severity or mildness of phenotype, or all factors being present.
• Ability of participant and their parent or guardian to understand and have willingness to sign a written informed consent and/or assent document.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Anyone unwilling to provide informed consent (for themselves as adults, on behalf of their children as minors, or on behalf of an adult who is unable to provide consent for themselves) or assent.
• Individuals who have undergone diagnostic testing for a genetic condition AND the test results were positive.
• Evidence that symptoms are secondary or caused by an undiagnosed condition that is unlikely to have a genetic cause.
• In the opinion of the investigator, participant has a condition that would preclude participation in the study by interfering with the participant s ability to engage in the required protocol evaluation and testing.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

University of Mauritius

Moka, Mauritius

RECRUITING

MeSH Terms

Conditions

Undiagnosed Diseases; Rare Diseases

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Neil A Hanchard, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Neil A Hanchard, M.D.

CONTACT

(301) 594-2151; neil.hanchard@nih.gov

Study Design

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

Study Record Dates

• First Submitted: September 13, 2024
• First Posted: September 19, 2024
• Study Start (Estimated): June 17, 2026
• Primary Completion (Estimated): August 21, 2034
• Study Completion (Estimated): August 21, 2034
• Last Updated: June 12, 2026

Record last verified: 2025-09-22

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)