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

NCT ID: NCT03962452

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-01
• Study Completion Date: 2025-02-01

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.

Conditions

Rare Diseases; Genetic Predisposition

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Mitochondrial disease

Unresolved index patients with suspected mitochondrial disease

Group Type: OTHER

Next Generation Sequencing (NGS)

Intervention Type: GENETIC

Determining the nucleic acid sequence

Interventions

Next Generation Sequencing (NGS)

Determining the nucleic acid sequence

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

Unclear diagnosis Suspected genetic cause of the disease

Exclusion Criteria

Missing informed consent of the patient/ legal guardian

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobias Haack, Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Tübingen

Locations

University Hospital Tübingen

Tübingen, , Germany

Countries

Germany

Other Identifiers

MiDiSeq

Identifier Type: -

Identifier Source: org_study_id