Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| CENTOGENE GmbH Rostock | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
The study aims to identify and systematically characterize Parkinson's patients with mutations in the LRRK2 gene. In about 90% of Parkinson's patients the cause of the disease is unclear. Based on current knowledge, it can be assumed that there are several causes and that the causes may be differ between patients; this makes research into the pathogenesis and possible therapies very difficult. In the case of monogenic Parkinson's diseases, which are due to changes in one gene (e.g. LRRK2), the function of the gene and possible disease mechanisms can be investigated. LRRK2-associated Parkinson's syndrome is clinically indistinguishable from idiopathic Parkinson's disease. It is inherited autosomal dominant, that means if one of the two gene copies is altered, the disease occurs. However, the disease does not occur in every mutation carrier, the penetrance is reduced and the mechanisms for that are still unclear. Ideally, knowledge of what influences penetrance could make it possible to exert targeted influence and prevent the disease. The comprehensive investigation of mechanisms of reduced penetrance but also of the effects of the mutation itself requires systematic investigations of as many affected persons as possible. We therefore aim to identify 4,000 people internationally, of them 1,500 with LRRK2-associated Parkinson's syndrome, 500 with LRRK2-mutations but without Parkinson's symptoms, 500 without mutations and without Parkinson's symptoms, 500 Parkinson patients with mutations in other genes than LRRK2 and 1,000 patients with idiopathic Parkinson's disease from the same populations. The participants will undergo a comprehensive survey on Parkinson's symptoms, concomitant diseases, environmental factors and medication and there is the possibility of more detailed genetic examinations. Participants will be asked to donate samples of blood, urine and household dust.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PD + LRRK2 | Patients with LRRK2-associated Parkinson's syndrome | ||
| no PD + LRRK2 | Participants with LRRK2-mutations but without Parkinson's symptoms | ||
| no PD + no LRRK2 | Participants without mutations and without Parkinson's symptoms | ||
| PD+ other than LRRK2 | Parkinson patients with mutations in other genes than LRRK2 | ||
| PD+ no LRRK2 | Patients with idiopathic Parkinson's disease |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Epidemiology of LRRK2-positive patients | Description of the frequency of all important clinical signs and symptoms including non-motor signs and factoring in the most important influencing factors such as sex, disease duration, and medication. We will report raw and corrected frequencies with 95% confidence intervals. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Analysis of penetrance of LRRK2 mutations | Penetrance rates (the proportion of individuals with LRRL2 mutation who exhibit clinical symptoms of Parkinson's disease) and phenotypes, and will try to predict penetrance in logistic regression models and quantify the influence of different factors impacting on penetrance. | 2 years |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Patients with Parkinson's disease or family members of participants with LRRK2 parkinsonism or members of a high risk population with an early PD onset, able to provide informed consent and equal or older than 18 years old.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Meike Kasten, Prof. Dr. | Contact | +4945131017518 | lipad.ropad@neuro.uni-luebeck.de |
| Name | Affiliation | Role |
|---|---|---|
| Christine Klein, Prof. Dr. | Institute of Neurogenetics, University of Luebeck | Principal Investigator |
| Meike Kasten, Prof. Dr. | Department of Psychiatry, University of Luebeck | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institute of Neurogenetics | Recruiting | Lübeck | Schelswig-Holstein | 23562 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34475849 | Derived | Usnich T, Vollstedt EJ, Schell N, Skrahina V, Bogdanovic X, Gaber H, Forster TM, Heuer A, Koleva-Alazeh N, Csoti I, Basak AN, Ertan S, Genc G, Bauer P, Lohmann K, Grunewald A, Schymanski EL, Trinh J, Schaake S, Berg D, Gruber D, Isaacson SH, Kuhn AA, Mollenhauer B, Pedrosa DJ, Reetz K, Sammler EM, Valente EM, Valzania F, Volkmann J, Zittel S, Bruggemann N, Kasten M, Rolfs A, Klein C; LIPAD Study Group. LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol: Deep Phenotyping of an International Genetic Cohort. Front Neurol. 2021 Aug 9;12:710572. doi: 10.3389/fneur.2021.710572. eCollection 2021. |
Not provided
Not provided
The Plan will be defined at later stages.
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| D020734 | Parkinsonian Disorders |
| ID | Term |
|---|---|
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Blood and urine samples will be biochemically analysed to determine factors leading to incomplete penetrance in LRRK2 positive carriers and biomarkers of Parkinson's disease.
In blood samples DNA and DNA methylation, RNA and proteins will be analysed. Urine samples will be analysed using NGS-based sequencing of the mitochondrial genome and search for mitochondrial DNA deletions.
Dust will be analysed toxicologically.
| Analysis of expressivity of LRRK2 mutations |
We will analyze expressivity (the degree in which a genotype is phenotypically expressed) of LRRK2 mutations. We will first define meaningful categories using our phenotypic data and then proceed to identify influencing factors. |
| 2 years |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |