Mitochondrial Diseases - Long-read Genome and Transcriptome Sequencing in Cases Unresolved After Short-read Genomics

The MiDiSeq project will enroll 20 unresolved index patients with suspected mitochondrial disease prioritized for genomic analysis.

Study Overview

• Status: Recruiting
• Conditions: Rare Diseases; Genetic Predisposition
• Intervention / Treatment: Genetic: Next Generation Sequencing (NGS)

Detailed Description

In the MiDiSeq (monocentric, prospective, open-label diagnostic) project, patients with suspected mitochondrial disease prioritized for i) high a priori probability for a genetic basis (e.g. positive family history) as well as availability of (ii) fibroblast cell lines with a biochemically defined phenotype, (iii) parental samples, (iv) short read whole genome and transcriptome datasets and (v) optional additional metabolomics and proteomics data.

The following questions will be leading the project:

i) to systematically benchmark different sequencing technologies to detect genetic and epigenetic variation and their impact on gene regulation.

(ii) to further develop algorithms for integrative analyses of different 'omics datasets.

(iii) to expand the analysis from coding Single-Nucleotide Variants (SNVs) and regulatory mutations to structural variants (SVs), repeat expansions and contractions, low complexity regions and epigenetic signatures.

(iv) to identify novel alterations and disease mechanisms. (v) to gain fundamental new insights into disease mechanisms and cellular biology.

(vi) to improve genetic diagnostics of future rare disease patients and to evaluate personalized therapeutic options.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olaf Rieß, Prof. Dr.; Phone Number: +49 7071 298; Email: olaf.riess@med.uni-tuebingen.de
• Study Contact Backup: Name: Tobias Haack, Dr.; Phone Number: 77696 +49 7071 298; Email: tobias.haack@med.uni-tuebingen.de

Study Locations

• Germany
  • Tübingen, Germany, 72076
    • Recruiting
    • University Hospital Tübingen
    • Contact: Tobias Haack, Dr.; Phone Number: 7696 +40 7071-297; Email: tobias.haack@med.uni-tuebingen.de
    • Contact: Olaf Rieß, Prof. Dr.; Phone Number: 2323 +40 7071-297; Email: olaf.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

Exclusion Criteria:

Missing informed consent of the patient/ legal guardian

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: Mitochondrial disease; Unresolved index patients with suspected mitochondrial disease	Genetic: Next Generation Sequencing (NGS); Determining the nucleic acid sequence

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Epi)Genetic variation	Number of (Epi)Genetic variation	1 Day

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen
• Investigators: Principal Investigator: Tobias Haack, Dr., University Hospital Tübingen

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Estimated): February 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: May 22, 2019
• First Submitted That Met QC Criteria: May 22, 2019
• First Posted (Actual): May 24, 2019

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; Mitochondrial disease; Genetic Predisposition; Omics; Epigenetic variation; Genetic variation; Next Generation Sequencing (NGS)
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Disease Attributes; Mitochondrial Diseases; Disease Susceptibility; Genetic Predisposition to Disease; Rare Diseases
• Other Study ID Numbers: MiDiSeq

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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