Parkinson's Disease and Parkinsonism
Conditions
Keywords
genetic Parkinson's disease, LRRK2
Brief summary
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.
Interventions
None listed
Sponsors
CENTOGENE GmbH Rostock
University of Luebeck
Study design
Observational model
OTHER
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
* Informed consent is obtained from the participant. * The participant is clinically diagnosed with Parkinson's disease or the individual is a family member of a participant with LRRK2 parkinsonism or is a member of a high risk population with an early PD onset. * The participant is equal to or older than 18 years old.
Exclusion criteria
* Inability to provide informed consent. * The participant is not suffering from Parkinson's disease or the individual is not a family member of a participant with LRRK2 parkinsonism or is not a member of a high risk population. * The participant is younger than 18 years old. * Previously enrolled in the study. * Participant in custody.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Epidemiology of LRRK2-positive patients | 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis of penetrance of LRRK2 mutations | 2 years | 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. |
| Analysis of expressivity of LRRK2 mutations | 2 years | 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. |
Countries
Germany
Contacts
Primary ContactMeike Kasten, Prof. Dr.
Outcome results
None listed