Identification of the Genetic Causes of Rare Diseases With Negative Exome Findings

Not Applicable

Recruiting

• Conditions: Rare Diseases; Genetic Predisposition to Disease
• Interventions: Genetic: WGS Diagnostic Blood take for genetic diagnostic.; Genetic: Hair collection

• Registration Number: NCT04315727
• Lead Sponsor: University Hospital Tuebingen

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.

Study Timeline

• Study First Submitted: 2020-03-17
• Study First Submitted QC: 2020-03-17
• Study First Posted: 2020-03-19
• Study Start: 2021-02-01
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-29
• Primary Completion: 2024-07
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study population	WGS Diagnostic Blood take for genetic diagnostic.	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).
Study population	Hair collection	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).

Primary Outcome Measures

Name	Time	Method
Identification of the molecular causes of unclear rare diseases	Day 1	Number of molecular causes

Secondary Outcome Measures

Name	Time	Method
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
Diagnoses for patients with rare diseases	Day 1	Number of diagnoses for patients with rare diseases

Trial Locations

Locations (1)

University Hospital Tübingen; 🇩🇪 Tübingen, Germany