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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03857880
Recruitment Status : Recruiting
First Posted : February 28, 2019
Last Update Posted : March 1, 2019
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:

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))

Condition or disease
Mitochondrial Diseases

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Study Type : Observational
Estimated Enrollment : 15 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identification of New Candidate Genes in Patients With Mitochondrial Disease by High Resolution Chromosome Analysis on DNA Chip
Actual Study Start Date : February 5, 2019
Estimated Primary Completion Date : August 5, 2020
Estimated Study Completion Date : August 5, 2020

Primary Outcome Measures :
  1. Variation of Number of copies [ Time Frame: 1 hour ]
    The variations in the number of copies by quantitative Polymerase Chain Reaction (PCR) targeted on the region of interest, previously identified on the High Resolution Chromosome Analysis on DNA Chip (CADC), whether it is in copy loss or copy gain.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patient with mitochondrial deseases

Inclusion Criteria:

  • Patients with mitochondrial disease (clinical and histological criteria)
  • Or Patients for whom an exome analysis has been performed, who are carriers of a pathogenic or probably pathogenic variant, in a heterozygous state, in an autosomal recessive transmission gene strongly candidate in view of the patient's clinic.
  • Or patients for whom exome analysis did not reveal any pathogenic variant explaining the phenotype

Exclusion Criteria:

  • People hospitalized without consent;
  • Phenotype not suggestive of mitochondrial disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03857880

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Contact: Morgane Plutino, PhD 4 92 03 64 55 ext +33

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Nice hospital Recruiting
Nice, France, 06000
Contact: Morgane PLUTINO, PhD    4 92 03 64 55 ext +33   
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
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Responsible Party: Centre Hospitalier Universitaire de Nice Identifier: NCT03857880    
Other Study ID Numbers: 18-AOI-07
First Posted: February 28, 2019    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mitochondrial Diseases
Metabolic Diseases