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

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Recruiting

CT.gov ID

NCT04315727

Collaborator

(none)

100

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Rare Diseases Genetic Predisposition to Disease	Genetic: WGS Diagnostic Blood take for genetic diagnostic. Genetic: Hair collection	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Feb 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Other: 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).	Genetic: WGS 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). Genetic: Hair collection Hair including root will be collected from the scalp (~15-20) and transferred to cultivation medium for the organoid cultivation

Arm

Intervention/Treatment

Other: 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).

Genetic: WGS 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).

Genetic: Hair collection

Hair including root will be collected from the scalp (~15-20) and transferred to cultivation medium for the organoid cultivation

Outcome Measures

Primary Outcome Measures

Identification of the molecular causes of unclear rare diseases [Day 1]
Number of molecular causes

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)