UW Undiagnosed Genetic Diseases Program

NCT04586075 | Recruiting

• 3 other identifiers: 2020-0700SMPHProtocol Version 10/28/2024
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

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

Keywords

genomics; genome sequencing; undiagnosed disease

Outcome Measures

Primary Outcomes (2)

• Number of New Disease Genes Discovered

  up to 5 years

• Number of Expanded Disease Gene Phenotypes

  up to 5 years

Secondary Outcomes (3)

• Number of Participants who are Diagnosed in 5 years

  up to 5 years

• Number of Participants Diagnosed per Analytical Technique

  up to 5 years

• Diagnostic Rate by Disease Presentation

  up to 5 years

Study Arms (1)

Undiagnosed Disease Group

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

Diagnostic Test: Trio Whole Genome Sequencing and Participant-Specific Research

Interventions

Trio Whole Genome Sequencing and Participant-Specific Research DIAGNOSTIC_TEST

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

Undiagnosed Disease Group

Eligibility Criteria

• Age: Up to 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

Males and females, ages 0-100 years, of all races and ethnicities, with an undiagnosed disease despite thorough evaluation by healthcare providers and having at least one objective finding. Subjects can come from all states of the US, as well as from other countries.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• University of Wisconsin Center for Human Genomics and Precision Medicine: collaborator

Study Sites (1)

University of Wisconsin School of Medicine and Public Health

Madison, Wisconsin, 53705, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be collected on all probands, parents, and participating affected family members unless they are refused by the participant or their collection would compromise participant safety. For a minority of patients, other biological samples may also be requested i.e., urine collection, saliva/buccal smears, and punch skin biopsies. Samples whose collection involves more than minimal risk (i.e., cerebrospinal fluid, bone marrow, liver, muscle, conjunctival, or renal biopsy) will be opportunistically obtained from residual material left after procedures performed for clinical purposes.

MeSH Terms

Conditions

Rare Diseases; Genetic Diseases, Inborn; Undiagnosed Diseases

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Bryn Webb, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jadin Heilmann

CONTACT

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

Study Design

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

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 14, 2020
• Study Start: July 16, 2021
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: June 4, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)