Whole Genome Trio Sequencing as a Standard Routine Test in Patients With Rare Diseases - "GENOME FIRST APPROACH"

NCT03954652 | Completed

• 1 other identifier: WG-Trio01
• Study Type: interventional
• Target: 1,350
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Rare Diseases; Genetic Predisposition

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Full genomic sequence analysis carried out by Whole Genome Sequencing (WGS)

  Number of genomic variants in disease and health parents by WGS (a Next-Generation Sequencing Technology, NGS)

  Day 1

Secondary Outcomes (2)

• Genome sequencing

  Day 1

• De novo alterations

  Day 1

Study Arms (3)

Cohort 1: Intellectual disability

OTHER

Genetic: WGS Diagnostic Blood take for genetic diagnostic.

Genetic: WGS-Diagnostic

Cohort 2 Retinal diseases

OTHER

Genetic: WGS Diagnostic Blood take for genetic diagnostic.

Genetic: WGS-Diagnostic

Cohort 3: Rare tumors in childhood

OTHER

Genetic: WGS Diagnostic Blood take for genetic diagnostic.

Genetic: WGS-Diagnostic

Interventions

WGS-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-seq.

Cohort 1: Intellectual disability; Cohort 2 Retinal diseases; Cohort 3: Rare tumors in childhood

Eligibility Criteria

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

You may qualify if:

• Unclear molecular cause of the disease
• Suspected genetic cause of the disease
• Healthy parents of those affected for trio analysis Cohort 1: IQ \< 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children.

You may not qualify if:

• Cohort 1: Toxic causes (drugs, infections) Cohort 2: patients with non-genetic forms of blindness Cohort 3: adult cancer, blood cancer
• Missing informed consent of the patient/ legal guardian
• Missing samples of both parents
• Previous WES or panel analysis-

Sponsors & Collaborators

• University Hospital Tuebingen: lead

Study Sites (1)

University Hospital Tübingen

Tübingen, 72076, Germany

Location

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, Prof. Dr.

  University Hospital Tübingen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort 1: IQ \< 70 with and without malformations, syndromic and non-syndromic Cohort 2: Retinitis pigmentosa, achromatopsy, Bardet-Biedl syndrome, Usher syndrome, congenital stationary night blindness, LCA, macula degeneration, rod/ cone dystrophies, opticus atrophy Cohort 3: Rare paediatric solid cancers as melanoma, carcinoma of the gastrointestinal tract, tumours of the salivary gland and pancreatic tumors in children. Plus: their respective parents

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: May 17, 2019
• Study Start: October 1, 2019
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: October 18, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)