Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT03954652 |
Other study ID # |
WG-Trio01 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
October 1, 2019 |
Est. completion date |
October 1, 2022 |
Study information
Verified date |
October 2022 |
Source |
University Hospital Tuebingen |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The GENOME FIRST APPROACH project will enroll patients (n = 450) and their healthy parents
with unclear molecular cause of the disease, suspected genetic cause of the disease and the
healthy parents of those affected for trio analysis (N in total 1350).
Description:
In the GENOME FIRST APPROACH (monocentric, prospective, open-label diagnostic) project,
patients with molecularly undiagnosed diseases will diagnostically be analyzed by Whole
Genome Sequencing (WGS)-trio analysis. The following questions will be leading the project:
Primary:
• Efficacy of WGS trio analysis in different clinical indications
Secondary:
- Systematically benchmark WGS analysis to detect genetic variations compared to WES and
single nucleotide polymorphism (SNP) array analysis,
- Expand the analysis from coding single-nucleotide variants (SNVs) to regulatory
mutations, structural variants (SVs), and low complexity regions,
- Validate the efficacy of clinical genome trio sequencing in a routine diagnostic
setting,
- Analyse whether 42x coverage has the potential to discover mosaicism as disease causing
mechanism,
- Further develop algorithms for integrative analyses of Trio-WGS data with Ribonucleic
acid- sequencing (RNA-seq),
- Identify de novo alterations and novel disease mechanisms,
- Gain fundamental new insights into disease mechanisms and cellular biology,
- Combine WGS with further Omics methods to improve genetic diagnostics of future rare
disease patients, and
- Explore overall financial costs and time to report conclusive data to the patients of
the Trio-WGS approach compared to traditional multistep diagnostic approaches using
single-gene, panel, whole-exome sequencing (WES) and chromosomal microarray (CMA) (SNP
array, array-based comparative genomic hybridization (arrayCGH)) analysis.
In addition, healthy parents of the subjects will be included in the project to perform
parent-child (trio) analyzes.