Genetic Predisposition to Disease, Rare Diseases
Conditions
Keywords
Rare Diseases, Genetic Predisposition, Whole Exome Sequencing, Whole Genome Sequencing (WGS), WGS-trio analysis
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. In addition, healthy parents of the subjects may be included in the study to perform parent-child (trio) analyses. In addition, phenotype and omics data will be shared within the University Hospital Tübingen, Germany and with external collaborators to improve the diagnostic rate of the patients included in the study. Storage of blood or tissue samples is not primary goal of this project, but may be necessary for further analyses.
Interventions
GENETICWGS Diagnostic Blood take for genetic diagnostic.
Blood sampling, shot clinical characterization, WGS based trio sequencing, NGS analysis and other omics analysis (transcriptomics, proteomics, metabolomics), functional cell biology studies (for example in fibroblast cultures), RNA Sequencing (RNA-seq).
GENETICHair collection
Hair including root will be collected from the scalp (\ 15-20) and transferred to cultivation medium for the organoid cultivation
Sponsors
University Hospital Tuebingen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Identification of the molecular causes of unclear rare diseases | Day 1 | Number of molecular causes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnoses for patients with rare diseases | Day 1 | Number of diagnoses for patients with rare diseases |
| Molecular characterization of putative disease causes | Day 1 | Identify molecular characterization of the putative disease causes |
| Patients receiving appropriate therapy after successful diagnosis | Day 1 | Number of patients receiving appropriate therapy after successful diagnosis |
Countries
Germany
Contacts
Primary ContactOlaf Rieß, Prof. Dr.
Backup ContactAndreas Dufke, PD Dr.
Outcome results
None listed