Combined Genome and RNA Sequencing for Genetic Diagnosis of Parkinsonism

NCT06576713 | Not Yet Recruiting

• 1 other identifier: 9320
• Study Type: interventional
• Target: 14
• Locations: 0 countries
• Sites: N/A

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 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.

Conditions

Parkinson's Disease

Outcome Measures

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.

  18 months

Secondary Outcomes (6)

• Genes implicated

  18 months

• Contribution of RNA sequencing

  18 months

• Genotype and Phenotype correlation

  18 months

• New genetic causes

  18 months

• Tolerance

  18 months

Study Arms (1)

Genome and RNA sequencing

EXPERIMENTAL

Diagnostic Test: Combiner whole genome and RNA sequencing

Interventions

Combiner whole genome and RNA sequencing DIAGNOSTIC_TEST

High-throughput DNA and RNA sequencing

Genome and RNA sequencing

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Extrapyramidal syndrome beginning before or at the age of 40 or associated with a family history:
• 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

You may not qualify if:

• \- 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
• Patient with Parkinson's syndrome associated with a specific diagnosis (genetic or non-genetic pathology: exposure to neuroleptics, toxic origin)
• Impossibility of providing the subject with informed information
• Subject under judicial protection
• Subject under guardianship or curatorship

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

Base Sequence

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena

Central Study Contacts

THOMAS WIRTH

CONTACT

03.88.12.80.19; thomas.wirth@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2024
• First Posted: August 29, 2024
• Study Start: December 1, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 29, 2024

Record last verified: 2024-08