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

Not Applicable

Completed

• Conditions: Genetic Predisposition; Rare Diseases
• Interventions: Genetic: Next Generation Sequencing (NGS)

• Registration Number: NCT03962452
• Lead Sponsor: University Hospital Tuebingen

Brief Summary

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

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 Timeline

• Study Start: 2019-03-01
• Study First Submitted: 2019-05-22
• Study First Submitted QC: 2019-05-22
• Study First Posted: 2019-05-24
• Primary Completion: 2024-02-01
• Study Completion: 2025-02-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Unclear diagnosis Suspected genetic cause of the disease

Exclusion Criteria

Missing informed consent of the patient/ legal guardian

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Mitochondrial disease	Next Generation Sequencing (NGS)	Unresolved index patients with suspected mitochondrial disease

Primary Outcome Measures

Name	Time	Method
(Epi)Genetic variation	1 Day	Number of (Epi)Genetic variation

Trial Locations

Locations (1)

University Hospital Tübingen; 🇩🇪 Tübingen, Germany