Lange, Lara M;
Levine, Kristin;
Fox, Susan H;
Marras, Connie;
Ahmed, Nazish;
Kuznetsov, Nicole;
Vitale, Dan;
... Global Parkinson’s Genetics Program (GP2); + view all
(2024)
The LRRK2 p.L1795F variant causes Parkinson's disease in the European population.
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Abstract
Pathogenic variants in the LRRK2 gene represent the most common cause of autosomal dominant Parkinson's disease (PD) worldwide. We identified the LRRK2 p.L1795F variant in 14 White/European ancestry PD patients, including two families with multiple affected carriers and seven additional affected individuals with familial PD using genotyping and sequencing data from more than 50,000 individuals through GP2, AMP-PD, PDGENEration, and CENTOGENE. All variant carriers were of White/European ancestry, and those with available genotyping data shared a common haplotype. The clinical presentation of p.L1795F carriers resembles that of other LRRK2 pathogenic variant carriers. Combined with published functional evidence showing strongly enhanced LRRK2 kinase activity, our findings provide conclusive evidence that the LRRK2 p.L1795F variant is pathogenic. It represents a rare cause of PD in the European population but needs to be included in genetic testing efforts and considered for ongoing gene-specific clinical trials.
| Type: | Working / discussion paper |
|---|---|
| Title: | The LRRK2 p.L1795F variant causes Parkinson's disease in the European population |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.21203/rs.3.rs-4772543/v1 |
| Publisher version: | http://dx.doi.org/10.21203/rs.3.rs-4772543/v1 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10198587 |
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