NCT03857880: ACPA HR

Identification of New Candidate Genes in Patients With Mitochondrial Disease by High Resolution Chromosome Analysis on DNA Chip

Completed Last updated 18 November 2023

What this trial tests

trial in Mitochondrial Diseases in 10 participants. Completed in 20 March 2022.

Timeline

20 September 2020

Primary endpoint
20 March 2022

20 March 2022

Quick facts

Lead sponsor	Centre Hospitalier Universitaire de Nice
Status	Completed
Study type	OBSERVATIONAL
Enrollment	10
Start date	20 September 2020
Primary completion	20 March 2022
Estimated completion	20 March 2022
Sites	1 location across France

Conditions studied

• Mitochondrial Diseases — all drugs for Mitochondrial Diseases →

Sponsor

Centre Hospitalier Universitaire de Nice

Who can join

1 and older, any sex, with Mitochondrial Diseases. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Mitochondrial diseases are complex diseases with great clinical and genetic heterogeneity and their diagnosis is difficult.

The Medical Genetics Department includes among its activities the diagnosis of these diseases. It has been a reference centre for mitochondrial diseases at the national level since 2006 and was recently approved under the call for projects "European Reference Network (ERN) for rare diseases", EURO-NMD, supported by the Nice University Hospital. The routine diagnostic strategy is based on high throughput mitochondrial DNA (mtDNA) sequencing analysis and a panel of 281 targeted "mitochondriopathies" genes. When these analyses are negative, an exome analysis (high throughput sequencing of all exons in the genome) can be performed in a research setting. To date, about 40% of the patients analysed remain without genetic diagnosis. Indeed, it does not allow to identify large variations of deletion, duplication or CNV (copy number variation) type. Moreover, targeting only exons, exome sequencing does not allow the detection of intronic or localized mutations in regulatory regions.

The identification of CNVs is made possible by chromosomal analysis on a DNA chip (CADC). This recognized technique is used routinely in the laboratory. The investigators use chips with a minimum resolution of approximately 13Kb for the genome-wide study of CNVs in patients with developmental disorders. However, this resolution is insufficient to detect rework events of the order of magnitude of an exon. There are high-resolution DNA chips, compatible with our platform, that would allow the investigators to more accurately visualize smaller rearrangements that could not be identified by exome analysis. The combined exome/CADC strategy has already proven its effectiveness in diagnosing various diseases by increasing yield.

In this context, the investigators aim to use this strategy in this non-interventional study on a series of 15 patients with mitochondrial disease who remain undiagnosed after analysis of mtDNA, gene panel and exome. They will test 2 types of patients:

* In the first series, whose disease is supposed to be transmitted in an autosomal recessive mode, only one heterozygous variant was identified in a gene already described in a comparable clinical picture. It is therefore possible that these patients are carriers on the second allele of a CNV, which the exome sequencing could not identify.
* In the second series, the exome analysis did not allow the identification of a single responsible gene (several candidate genes without any certainty on the pathogenicity of the gene(s) or variant(s))

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.