Recruiting

Genetic Diseases

Sponsor:

University of Wisconsin, Madison

Code:

NCT04586075

Conditions

Rare Diseases

Genetic Disease

Undiagnosed Disease

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Interventions

Trio Whole Genome Sequencing and Participant-Specific Research

Study Details

Brief summary:

The primary purpose of this study is to discover new disease genes for rare Mendelian disorders and its secondary purpose include diagnosing people with rare genetic disorders that have not been previously diagnosed through conventional clinical means, learning more about the pathobiology of genetic disorders, and developing novel diagnostic technologies and analytics. 500 participants with undiagnosed and suspected genetic disorders will be recruited.

Conditions

Rare Diseases

Genetic Disease

Undiagnosed Disease

Study ID

NCT04586075

Start date

Jul 16, 2021

Status verified date

May, 2026

Completion date

Oct, 2030

Anticipated

Primary completion date

Oct, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • The applicant has a condition that remains undiagnosed despite thorough evaluation by healthcare providers (including clinical genetic testing).
  • The applicant has at least one objective finding that is likely to have an identifiable genetic etiology.
  • The applicant likely has a currently undescribed/new genetic condition or a known genetic condition associated with a novel gene.
  • The applicant/legal guardian agrees to the collection, storage and recurrent sharing of coded information and biomaterials for research and diagnostic purposes both within and outside of the University of Wisconsin-Undiagnosed Diseases Program (UW-UDP)
  • The applicant/legal guardian agrees to receive secondary findings from genetic testing.
  • The applicant/legal guardian has sufficient proficiency in English to understand the consent.

Exclusion Criteria:

  • The applicant already has a diagnosis that explains the objective findings.
  • A specific diagnosis is suspected and a standard clinical workup performed by the referring/primary care provider would be appropriate.
  • The UW-UDP is unlikely to improve on the comprehensive workup the applicant has already received.
  • The applicant's symptoms are likely multifactorial or due to a non-genetic cause.

Study Design

Enrollment

1000 participants

Anticipated

Interventions and Outcome Measures

Arms

Undiagnosed Disease Group

Blood or other relevant biological samples obtained from consenting research subjects will be banked and extracted for DNA and RNA.

Interventions

Trio Whole Genome Sequencing and Participant-Specific Research

The initial evaluation begins with short-read genome sequencing of DNA extracted from blood of affected individual(s) and participating family members (The most common approach will be trio whole genome sequencing, which involves the affected child + their parents).

Additional evaluation may include: functional assessments, animal modeling, reverse phenotyping (may require an interim visit), epigenetic profiling, or clinical database matching through selective sharing of coded patient data with external collaborators (e.g., via Matchmaker Exchange and Phenome Central), long read genome sequencing, de novo genome assembly, RNA sequencing, and novel bioinformatics analyses

Primary outcome measure

  • Number of New Disease Genes Discovered [ Time Frame: up to 5 years ]
  • Number of Expanded Disease Gene Phenotypes [ Time Frame: up to 5 years ]

Central Contacts and Locations

Central contacts

Research Coordinator

(608) 263-5877

Locations

University of Wisconsin School of Medicine and Public Health

Recruiting

Madison, Wisconsin, United States, 53705

Contacts

Study Coordinator

(608) 263-5877research@CHGPM.wisc.edu

Principal Investigator:

Bryn Webb, MD

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

May 29, 2026

Last verified

May, 2026

Keywords

  • genomics
  • genome sequencing
  • undiagnosed disease

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-05-29.