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

Sponsor

University Hospital Tuebingen (Other)

Overall Status

Recruiting

CT.gov ID

NCT03962452

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Rare Diseases Genetic Predisposition	Genetic: Next Generation Sequencing (NGS)	N/A

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:

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 Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

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

Actual Study Start Date :

Mar 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Other: Mitochondrial disease Unresolved index patients with suspected mitochondrial disease	Genetic: Next Generation Sequencing (NGS) Determining the nucleic acid sequence

Arm

Intervention/Treatment

Other: Mitochondrial disease

Unresolved index patients with suspected mitochondrial disease

Genetic: Next Generation Sequencing (NGS)

Determining the nucleic acid sequence