Genetic Disease
Conditions
Brief summary
Prospective observational study to further understand the value that a multi-omic approach has in individuals with a multi system, early onset disorder that does not have a molecular diagnosis by whole genome sequencing.
Detailed description
Understand the value and utilization of integrated multi-omics, in multi-system early onset disorders that have failed to yield findings by whole genome sequencing
Interventions
None listed
Sponsors
Medical College of Wisconsin
Illumina, Inc.
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* Undiagnosed probands must meet all of the following: 1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, their parent must have these abilities) 2. Proband between the ages of 12 months and 65 years 3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed) 4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years 5. A high prior probability of a multi-system early onset undiagnosed genetic disorder based on an expert medical assessment 6. Clinical WGS that did not yield a definitive diagnosis 7. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American 8. Must be willing to have blood, urine and fecal samples taken to include participating family members Diagnosed probands must meet all of the following: 1. Must be able to understand and sign an informed consent and speak, read, and write in their native language (if the subject is a minor, its Parent or Legally Authorized Representative must have these abilities). 2. Proband between the ages of 12 months and 65 years 3. Study consent and participation of at least two unaffected family members (biological parents preferred. One biological parent and unaffected sibling allowed) 4. If applicable, unaffected sibling must be between the ages of 12 months and 65 years 5. Known genetic cause(s) of disease, disorder, or phenotypic defect through prior clinical whole genome sequencing 6. It is preferred but not required that ancestry is from an under-represented population in current clinical genetic and translational research data repositories, especially African American, Asian American and Native American 7. Must be willing to have blood, urine and fecal samples taken to include participating family members
Exclusion criteria
* Undiagnosed probands must not meet any: 1. Known non-genetic cause(s) of disease, disorder, or phenotypic defect 2. Principal Investigator decides that the study is not in the best interest of the proband Diagnosed probands must not meet any: 1\. Principal Investigator decides that the study is not in the best interest of the proband
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Based on analysis of data from completed clinical utility evaluation surveys following receipt of study results by the PI, assess whether a patient's change of management resulted from the multi-omic results | 120 Days | Understand the value and utilization of integrated multi-omics, in multi-system early onset disorders that have failed to yield findings by whole genome sequencing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of diagnoses yielded by each of the different orthogonally confirmed assay results | 120 Days | Assess the number of new diagnoses yielded by each approach |
| Analyze data from completed clinical utility evaluation surveys; number of patients with change of management and whether the change was due to a diagnosis yielded by multiomic results | 120 Days | Analyze the clinical utility derived from a diagnosis |
| Data utilization of multi-omic dataset for scientific community | 120 Days | Establish a multi-omic reference dataset from resource limited populations that can be used by the scientific community |
Countries
United States
Outcome results
None listed