Ignite Creation Date:
2024-05-06 @ 12:49 PM
Last Modification Date:
2024-10-26 @ 1:04 PM
Study NCT ID:
NCT03857880
Status:
COMPLETED
Last Update Posted:
2023-11-18
First Post:
2019-02-27
Brief Title:
Identification of New Candidate Genes in Patients With Mitochondrial Disease by High Resolution Chromosome Analysis on DNA Chip
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Centre Hospitalier Universitaire de Nice
Study Overview
Official Title:
Identification of New Candidate Genes in Patients With Mitochondrial Disease by High Resolution Chromosome Analysis on DNA Chip
Status:
COMPLETED
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ACPA HR
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 exomeCADC 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 genes or variants
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 exomeCADC 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 genes or variants
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None