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

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

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).

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.

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