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

NCT ID: NCT04315727

Last Updated: 2023-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-01

Study Completion Date

2024-12-31

Brief Summary

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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

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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.

Conditions

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Rare Diseases Genetic Predisposition to Disease

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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).

Group Type OTHER

WGS Diagnostic Blood take for genetic diagnostic.

Intervention Type GENETIC

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).

Hair collection

Intervention Type GENETIC

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

Interventions

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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).

Intervention Type GENETIC

Hair collection

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

Intervention Type GENETIC

Eligibility Criteria

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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
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital Tuebingen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Olaf Rieß

Role: STUDY_DIRECTOR

University Hospital Tübingen

Locations

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University Hospital Tübingen

Tübingen, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Tübingen

Tübingen, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Olaf Rieß, Prof. Dr.

Role: CONTACT

+49 7071 29 ext. 72323

Andreas Dufke, PD Dr.

Role: CONTACT

+49 7071 29 ext. 72190

Facility Contacts

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Olaf Rieß, Prof. Dr.

Role: primary

+49 7071 29 ext. 72323

Andreas Dufke, PD Dr.

Role: backup

+49 7071 29 ext. 72190

Olaf Rieß, Prof. Dr.

Role: primary

+49 7071 29 ext. 72323

Andreas Dufke, PD Dr.

Role: backup

+49 7071 29 ext. 72190

Other Identifiers

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GENOME +

Identifier Type: -

Identifier Source: org_study_id