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

University Hospital Tuebingen

Status: Completed

Conditions: Genetic Predisposition; Rare Diseases

Treatments: Genetic: Next Generation Sequencing (NGS)

Study type: Interventional

Funder types: Other

Identifiers

NCT03962452

MiDiSeq

Details and patient eligibility

About

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

Full 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.

Enrollment: 20 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

Unclear diagnosis Suspected genetic cause of the disease

Exclusion criteria

Missing informed consent of the patient/ legal guardian

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

Mitochondrial disease

Other group

Description:

Unresolved index patients with suspected mitochondrial disease

Treatment:

Genetic: Next Generation Sequencing (NGS)