Description
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.
