Identification of the Genetic Causes of Rare Diseases With Negative Exome Findings
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Enrollment
- 100
- Locations
- 2
- Primary Endpoint
- Identification of the molecular causes of unclear rare diseases
Study Overview
Brief Summary
The GENOME + project will enroll patients (n = ca. 100) and their healthy parents with unclear molecular cause of the disease, suspected genetic cause of the disease and previous detailed molecular analysis like Whole Exome Sequencing (WES) did not lead to the identification of the disease causing mechanism. As well healthy parents of those affected for trio analysis (exception of one parent is not available for the study).
Detailed Description
In the GENOME+ study (monocentric, prospective, open-label diagnostic study), patients with molecularly undiagnosed diseases will diagnostically be analyzed by means of omics technologies or re-analyzed using existing datasets. The following questions will be leading the study:
Primary:
• Identification of the molecular causes of unclear rare diseases
Secondary:
- Improve number of diagnoses for patients with rare diseases
- Further characterization of the identified putative disease causes
- Increase number of patients receiving appropriate therapy after successful diagnosis.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Unclear diagnosis
- •Suspected genetic cause of the disease
- •Previous detailed molecular analysis like Whole Exome Sequencing (WES) did not lead to the identification of the disease causing mechanism
- •Healthy parents of those affected for trio analysis (exception of one parent is not available for the study)
Exclusion Criteria
- •Missing informed consent of the patient and her/his parents
Arms & Interventions
Study population
Both underage and adult persons (male and female) with diagnostically unsolved rare diseases who have been or are included into diagnostic care at the University Hospital Tübingen, Germany (UKT) and who are suspected of having a genetic cause of the disease. In addition, healthy parents of volunteers will be recruited if available to facilitate Trio studies.
Study related procedures: Blood sampling, hair collection, anamnesis including pedigree, Next Generation Sequencing (NGS) analysis and other omics analysis (transcriptomics, proteomics, metabolomics), functional cell biology studies (for example in fibroblast cultures, organoid cultivation).
Intervention: WGS Diagnostic Blood take for genetic diagnostic. (Genetic)
Study population
Both underage and adult persons (male and female) with diagnostically unsolved rare diseases who have been or are included into diagnostic care at the University Hospital Tübingen, Germany (UKT) and who are suspected of having a genetic cause of the disease. In addition, healthy parents of volunteers will be recruited if available to facilitate Trio studies.
Study related procedures: Blood sampling, hair collection, anamnesis including pedigree, Next Generation Sequencing (NGS) analysis and other omics analysis (transcriptomics, proteomics, metabolomics), functional cell biology studies (for example in fibroblast cultures, organoid cultivation).
Intervention: Hair collection (Genetic)
Outcomes
Primary Outcomes
Identification of the molecular causes of unclear rare diseases
Time Frame: Day 1
Number of molecular causes
Secondary Outcomes
- Patients receiving appropriate therapy after successful diagnosis(Day 1)
- Molecular characterization of putative disease causes(Day 1)
- Diagnoses for patients with rare diseases(Day 1)