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NCT Number: NCT06060184

Initiative for Clinical Long-read Sequencing

The study aims to comprehensively introduce Long-read Genome sequencing (LR-GS) based genetic testing into clinical routine. In order to demonstrate the superiority of untargeted LR-GS over Short-read Genome sequencing (SR-GS) to establish firm genetic diagnoses, the investigators will rely on a multi-center "Translate Nationale Aktionsbündnis für Menschen mit Seltenen Erkrankungen" (Translate National Action Alliance for People with Rare Diseases Germany, TNAMSE) cohort of unsolved patients with neurological, neurodevelopmental, and imprinting disorders that is expectedly enriched for complex genomic variation. Within the framework of genomDE, the investigators will then implement, for the first time, LR-GS in the diagnostic work-up of a prospective cohort of patients with a broad range of clinical indications including rare diseases and cancer predisposition.

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Key information

Conditions

Genetic Predisposition Disease Attributes Disease Susceptibility Genetic Predisposition to Disease Pathologic Processes Pathological Conditions, Signs and Symptoms Rare Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

The proposed study aims to develop a blueprint for the implementation of LR-GS in clinical diagnostics. Hence Standard Operating Procedures (SOPs) and guidelines for library preparation, bioinformatic analysis, and clinical interpretation will be compiled. Furthermore, the investigators intend to develop an open source 'gold standard' bioinformatics pipeline, addressing all relevant types of genomic alterations, thus providing the bioinformatic basis for a streamlined implementation of LR-GS at other sites. In addition to in-depth phenotype information the availability of SR-GS will be instrumental to benchmark the ability to detect different types of genomic variation. Additional relevant issues for genetic testing such as variant calling in difficult-to-map genomic regions, detection of genomic methylation patterns, characterization of repeat expansion and duplicated genes, and haplotype-phased genome de novo assembly will be addressed. Moreover, based on the strong background in Artificial Intelligence (AI) driven variant prioritization in the consortium, the investigators aim to implement and/or develop tools that enable an efficient prioritization of disease-causing variants. Beyond the usage within the context of the proposed study, generated datasets will be made available according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles for national (German Human Genome-Phenome Archive, GHGA) and international (European Genome-Phenome Archive, EGA, Genome-Phenome Analysis Platform, GPaP) data repositories. the investigators aim to establish a population scale reference dataset for Structural variants (SV), which is absolutely mandatory in the context of rare disease diagnostics.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Unclear molecular cause of the disease (retrospective cohort)
  • Indication for genome diagnostics (prospective cohort; e.g. within the initiative for genomic medicine (genomDE) based on §64e SGB V)
  • Suspected genetic cause of the disease

Exclusion criteria

  • Missing informed consent of the patient or legal guardian

Treatment and study plan

Next-Generation Sequencing (NGS)

Genetic

Sequencing of genomes (Long read NGS)

Primary outcomes

  1. Number of patients with Rare Disease (RD) or cancer predisposition syndromes with confirmed diagnosis by LR-GS compared to previous diagnostic methods including SR-GS

    Time frame: Day 1

    A molecular diagnosis is considered confirmed when likely pathogenic or pathogenic variants are identified according to the American College of Medical Genetics and Genomics (ACMG). classification.

Study contacts

Contact information is provided by the study sponsor or research team.

Olaf Rieß, Prof. Dr.

CONTACT

[email protected]

+49 7071 29 ext. 72288

Tobias Haack, Dr.

CONTACT

[email protected]

+49 7071 29 ext. 77696

Sponsors and collaborators

Lead sponsor

University Hospital Tuebingen

Other

Collaborators

  • Charite University, Berlin, Germany
  • Medical University of Hannover
  • RWTH Aachen University

Registry information

Official study title

Initiative for Clinical Long-read Sequencing - Towards Implementation of Long-read Genome Sequencing in Routine Diagnostics

Acronym: IonGER

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Sep 29, 2023
Registry last updated
Sep 29, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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