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

NCT04315727 | Unknown

• 1 other identifier: GENOME +
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

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).

Conditions

Rare Diseases; Genetic Predisposition to Disease

Keywords

Rare Diseases; Genetic Predisposition; Whole Exome Sequencing; Whole Genome Sequencing (WGS); WGS-trio analysis

Outcome Measures

Primary Outcomes (1)

• Identification of the molecular causes of unclear rare diseases

  Number of molecular causes

  Day 1

Secondary Outcomes (3)

• Diagnoses for patients with rare diseases

  Day 1

• Molecular characterization of putative disease causes

  Day 1

• Patients receiving appropriate therapy after successful diagnosis

  Day 1

Study Arms (1)

Study population

OTHER

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.; Genetic: Hair collection

Interventions

WGS Diagnostic Blood take for genetic diagnostic. 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).

Study population

Hair collection GENETIC

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

Study population

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

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

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (2)

University Hospital Tübingen

Tübingen, 72076, Germany

NOT YET RECRUITING

University Hospital Tübingen

Tübingen, 72076, Germany

RECRUITING

MeSH Terms

Conditions

Rare Diseases; Genetic Predisposition to Disease

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Susceptibility

Study Officials

• Olaf Rieß

  University Hospital Tübingen

  STUDY DIRECTOR

Central Study Contacts

Olaf Rieß, Prof. Dr.

CONTACT

+49 7071 29; olaf.riess@med.uni-tuebingen.de

Andreas Dufke, PD Dr.

CONTACT

+49 7071 29; andreas.dufke@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2020
• First Posted: March 19, 2020
• Study Start: February 1, 2021
• Primary Completion: July 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 29, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: Data will become available after analysis and unlimited.
• Access Criteria: Authorized users within the participating organizations

Locations

DE (2)