PROTECTMOVE

Identifying Parkinson’s disease penetrance-modifying factors in the population-based Cooperative Health Research in South Tyrol (CHRIS) cohort

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  • Project duration: November 2016 - June 2023
  • Project status:
    Approval by the Scientific Committee
  • Website: http://protect-move.de/

Genes causative for recessively inherited Parkinson’s disease (PD) include Parkin and PINK1; rare homozygous mutations in these genes result in definite symptom expression. On the other hand, heterozygous mutations – a relatively common occurrence – may predispose to PD in a dominant manner with highly reduced penetrance. The largest described pedigree of Parkin mutation carriers (n=77) originates from South Tyrol and includes numerous heterozygous carriers of Parkin mutations who develop overt symptoms of Parkinson’s disease (PD), while others may have prodromal, or no obvious symptoms. In this project, we aim to dissect out the factors that modify the penetrance of these variants, using additional Parkin mutation carriers identified in the Cooperative Health Research in South Tyrol (CHRIS) study (comprising n=13,490 individuals from the same geographical region). By testing whether factors that influence mitochondrial function can alter penetrance of nuclear mutations, we observed an increased burden of heteroplasmic mtDNA mutations in affected vs. unaffected heterozygous Parkin and PINK1 (Phosphatase and tensin homolog-induced putative kinase 1) mutation carriers, which might explain the phenotypic (clinical, sub-clinical) discordance in these individuals with similar nuclear genetic background. However, the specificity of mtDNA variation and additional factors as penetrance markers and the molecular pathways involved ultimately leading to neurodegeneration, require further investigation with larger datasets. Within the DFG funded project ProtectMove, we are examining these questions. In 2020 DFG funding was renewed for further three years.

Publications
Molecular investigation of apparently healthy heterozygous Parkin mutation carriers
Castelo-Rueda MP, Zanon A, Gilmozzi V, Klein C, Pramstaller PP, Hicks AA, Pichler I (2021)
Presentation/Speech

Conference: 22nd International Congress of Parkinson's Disease and Movement Disorders International Congress of Parkinson's Disease and Movement Disorders | virtual | 17.9.2021 - 21.9.2021

Investigating the causal role of Inflammation on Parkinson's disease by a bidirectional Mendelian Randomization Approach
Bottigliengo D, Foco L, Seibler P, Klein C, König I R, Del Greco M F (2021)
Conference proceedings article

Conference: 2021 IGES Annual Meeting | | 13.10.2021 - 16.9.2021

More information: https://www.geneticepi.org/iges-2021

Investigating the causal role of Inflammation on Parkinson's disease by a bidirectional Mendelian Randomization Approach
Bottigliengo D, Foco L, Seibler P, Klein C, König I R, Del Greco M F (2021)
Conference proceedings article

Conference: XI Congresso Nazionale SISMEC | Bari | 15.9.2021 - 18.9.2021

More information: https://sismecbari2021.it/

Frequency of Heterozygous Parkin (PRKN) Variants and Penetrance of Parkinson's Disease Risk Markers in the Population-Based CHRIS Cohort
Castelo Rueda MP, Raftopoulou A, Gögele M, Borsche M, Emmert D, Fuchsberger C, Hantikainen EM, Vukovic V, Klein C, Pramstaller PP, Pichler I, Hicks AA (2021)
Journal article
Frontiers in Neurology

More information: https://doi.org/10.3389/fneur.2021.706145

https://doi.org/10.3389/fneur.2021.706145

The impact of instruments selection on Mendelian Randomization results: a case study
Bottigliengo D, Caliebe A, König IR, Del Greco MF (2021)
Conference proceedings article

Conference: 42nd Annual Conference of the International Society for Clinical Biostatistics (ISCB42) Conference | Lyon | 18.7.2021 - 22.9.2021

More information: http://www.iscb2021.info/en

The role of mitochondria in modifying penetrance of Parkin gene variants
Castelo MP, Trinh J, Zanon A, Rainer J, Bauer P, Kandaswamy KK, Werber M, Rolfs A, Grunewald A, Borsche M, Lohmann K, Klein C, Pramstaller PP, Pichler I, Hicks A (2019)
Presentation/Speech

Conference: International Congress of Parkinson's Disease and Movement Disorders | Nice | 22.9.2019 - 26.9.2019

http://hdl.handle.net/10863/12975

Partner
University of Lübeck, Institute of Neurogenetics
University of Luxembourg, Luxembourg Centre for Systems Biomedicine
Project Team
1 - 6

Projects

1 - 4
Project

EPICIR

Epigenetics of Immunity in Cancer

Duration: September 2019 - October 2021Funding:
Italy-Austria 2014-2020 (EUTC / EU funding / Project)

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Institute's Projects

Institute
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Eurac Research is a private research center based in Bolzano (South Tyrol) with researchers from a wide variety of scientific fields who come from all over the globe. Together, through scientific knowledge and research, they share the goal of shaping the future.

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Our research addresses the greatest challenges facing us in the future: people need health, energy, well-functioning political and social systems and an intact environment. These are complex questions, and we are seeking the answers in the interaction between many different disciplines. In so doing, our research work embraces three major themes: regions fit for living in, diversity as a life-enhancing feature, a healthy society.

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