Combined Genome and RNA Sequencing for Genetic Diagnosis of Parkinsonism
ConditionParkinson's Disease
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Hospital, Strasbourg, France
About this trial
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 Parkinson's disease.
In this work,investigators aimed at elucidating the missing genetic causes of parkinsonism through the application of combined RNA and whole genome sequencing.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Dopaminergic denervation proven by ioflupane brain scintigraphy (DaTscan®)
DNAs from both asymptomatic parents available in biobank
Subject affiliated to a social protection health insurance scheme or beneficiary or beneficiary
Subject able to understand the objectives and risks related to the research and to give dated and signed informed consent
Disqualifiers
- Contraindication for performing a superficial skin biopsy provided for by the protocol
Molecular cause of parkinsonism previously identified
Absence of prior genetic exploration by high-throughput DNA sequencing
Patient with late-onset sporadic parkinsonian syndrome (> 40 years) without family history
Trial design
Design model
Single group
Treatments tested in this trial
Combiner whole genome and RNA sequencing
Diagnostic testHigh-throughput DNA and RNA sequencing
Treatment groups
14 Participants
are divided into 1 treatment groupGroup A: Genome and RNA sequencingExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Genetic diagnosis rate
To estimate the rate of genetic diagnoses obtained by genome sequencing coupled with RNA sequencing within a cohort of patients presenting with early onset or familial parkinsonian syndromes without molecular diagnosis.
Time frame
18 monthsSecondary outcomes
1
Genes implicated
Estimate the proportion of patients carrying pathogenic or probably pathogenic variants in each of the genes identified in this work
Time frame
18 months2
Contribution of RNA sequencing
Estimate the proportion of pathogenic or probably pathogenic variants detected secondarily thanks to the contribution of RNA sequencing and not identified by analysis of the genome taken in isolation.
Time frame
18 months3
Genotype and Phenotype correlation
Estimate the proportion of patients presenting specific clinical, biological and imaging characteristics for each identified genetic cause (genotype/phenotype correlation).
Time frame
18 months4
New genetic causes
Describe new molecular mechanisms of parkinsonian syndromes.
Time frame
18 monthsSponsors and contacts
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Source ClinicalTrials.gov