Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06576713
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-08-26
Brief Title:
Combined Genome and RNA Sequencing for Genetic Diagnosis of Parkinsonism
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Identification of the Missing Genetic Causes of Parkinsonian Syndromes a Combined Approach by Genome and RNA Sequencing
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ParkOmic
Brief Summary:
Despite the increasing availability and advances in the analysis of high-throughput DNA sequencing the majority of patients with early-onset or familial parkinsonism remain without a molecular diagnosis
Studying the genetic forms of parkinsonian syndromes presents numerous clinical scientific and therapeutic interests In clinical practice identifying the genetic cause in a patient allow to provide genetic counseling and estimate the risk of recurrence in their relatives Establishing correlations between the genotype and phenotype of patients with genetically determined parkinsonism allow to better anticipate the evolution of the disease or even to highlight biomarkers during the presymptomatic phases Finally the proteins encoded by the genes implicated in familial parkinsonism represent potential therapeutic targets likely to be modulated by neuroprotective pharmacological agents even in sporadic Parkinsons disease
In this workinvestigators aimed at elucidating the missing genetic causes of parkinsonism through the application of combined RNA and whole genome sequencing
Studying the genetic forms of parkinsonian syndromes presents numerous clinical scientific and therapeutic interests In clinical practice identifying the genetic cause in a patient allow to provide genetic counseling and estimate the risk of recurrence in their relatives Establishing correlations between the genotype and phenotype of patients with genetically determined parkinsonism allow to better anticipate the evolution of the disease or even to highlight biomarkers during the presymptomatic phases Finally the proteins encoded by the genes implicated in familial parkinsonism represent potential therapeutic targets likely to be modulated by neuroprotective pharmacological agents even in sporadic Parkinsons disease
In this workinvestigators aimed at elucidating the missing genetic causes of parkinsonism through the application of combined RNA and whole genome sequencing
Detailed Description:
Investigators selected 14 patients with early-onset parkinsonism for whom no variant of certain pathogenicity had been identified after exome sequencing
Patients and their relatives will have a blood sample collection following the inclusion visit for DNA extraction patients will receive a skin biopsy for fibroblast culture and RNA extraction for RNA sequencing The genome sequencing will be performed on an Illumina HiSeq4000 sequencer
Investigators will also perform skin biopsies on patients for fibroblast cultures in order to extract RNA for RNA sequencing The choice of fibroblast analysis for the study of the transcriptome is justified by the fact that genes expressed in the brain likely to be associated with neurodegenerative diseases are more frequently expressed in the skin than in the other clinically accessible tissues such as blood Skin biopsies will be performed by the referring clinicians and RNA extraction will be carried out using the Quiagen RNeasy kit
Transcriptome analysis by RNA sequencing including sequencing and bioinformatics processing of data including detection of aberrant splicing LeafCutter aberrant expressions DESeq and identification of variants GATK Varank will also be carried out Genome data will be integrated with data from RNA sequencing Investigators plan to analyze all 14 patients according to this strategy
Patients and their relatives will have a blood sample collection following the inclusion visit for DNA extraction patients will receive a skin biopsy for fibroblast culture and RNA extraction for RNA sequencing The genome sequencing will be performed on an Illumina HiSeq4000 sequencer
Investigators will also perform skin biopsies on patients for fibroblast cultures in order to extract RNA for RNA sequencing The choice of fibroblast analysis for the study of the transcriptome is justified by the fact that genes expressed in the brain likely to be associated with neurodegenerative diseases are more frequently expressed in the skin than in the other clinically accessible tissues such as blood Skin biopsies will be performed by the referring clinicians and RNA extraction will be carried out using the Quiagen RNeasy kit
Transcriptome analysis by RNA sequencing including sequencing and bioinformatics processing of data including detection of aberrant splicing LeafCutter aberrant expressions DESeq and identification of variants GATK Varank will also be carried out Genome data will be integrated with data from RNA sequencing Investigators plan to analyze all 14 patients according to this strategy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None