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).

Study Overview

• Status: Recruiting
• Conditions: Genetic Predisposition to Disease; Rare Diseases
• Intervention / Treatment: Genetic: WGS Diagnostic Blood take for genetic diagnostic.; Genetic: Hair collection

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 Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andreas Dufke, PD Dr.; Phone Number: 72190 +49 7071 29; Email: andreas.dufke@med.uni-tuebingen.de
• Study Contact Backup: Name: Olaf Rieß, Prof. Dr.; Phone Number: 72323 +49 7071 29; Email: olaf.riess@med.uni-tuebingen.de

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Not yet recruiting
    • University Hospital Tübingen
    • Contact: Andreas Dufke, PD Dr.; Phone Number: 72190 +49 7071 29; Email: andreas.dufke@med.uni-tuebingen.de
    • Contact: Olaf Rieß, Prof. Dr.; Phone Number: 72323 +49 7071 29; Email: olaf.riess@med.uni-tuebingen.de
  • Tübingen, Germany, 72076
    • Recruiting
    • University Hospital Tübingen
    • Contact: Andreas Dufke, PD Dr.; Phone Number: 72190 +49 7071 29; Email: andreas.dufke@med.uni-tuebingen.de
    • Contact: Olaf Rieß, Prof. Dr.; Phone Number: 72323 +49 7071 29; Email: 0laf.riess@med.uni-tuebingen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the molecular causes of unclear rare diseases	Number of molecular causes	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnoses for patients with rare diseases	Number of diagnoses for patients with rare diseases	Day 1
Molecular characterization of putative disease causes	Identify molecular characterization of the putative disease causes	Day 1
Patients receiving appropriate therapy after successful diagnosis	Number of patients receiving appropriate therapy after successful diagnosis	Day 1

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Study Director: Olaf Rieß, University Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 17, 2020
• First Submitted That Met QC Criteria: March 17, 2020
• First Posted (Actual): March 19, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Rare Diseases; Genetic Predisposition; Whole Exome Sequencing; Whole Genome Sequencing (WGS); WGS-trio analysis
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Disease Susceptibility; Genetic Predisposition to Disease; Rare Diseases
• Other Study ID Numbers: GENOME +

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The GENOME+ study will provide data in a pseudonymized manner to national and international databases set up to increase the diagnostic yield through advanced analysis tools and matchmaking against other cohorts
• IPD Sharing Time Frame: Data will become available after analysis and unlimited.
• IPD Sharing Access Criteria: Authorized users within the participating organizations
• IPD Sharing Supporting Information Type: ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No