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

University Hospital Tuebingen

Status: Enrolling

Conditions: Genetic Predisposition to Disease; Rare Diseases

Treatments: Genetic: WGS Diagnostic Blood take for genetic diagnostic.; Genetic: Hair collection

Study type: Interventional

Funder types: Other

Identifiers

NCT04315727

GENOME +

Details and patient eligibility

About

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).

Full 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.

Enrollment: 100 estimated patients

Sex: All

Volunteers: No 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)

Exclusion criteria

• Missing informed consent of the patient and her/his parents

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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100 participants in 1 patient group

Study population

Other group

Description:

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).

Treatment:

Genetic: WGS Diagnostic Blood take for genetic diagnostic.

Genetic: Hair collection