Objective: This study aimed to identify the genetic landscape of early-onset Parkinson’s Disease (EOPD) in a cohort from a referral center in Brazil.

Background: Parkinson’s disease (PD) is a complex multifactorial neurodegenerative disease. The influence of genetics is a major subject of interest with a stronger impact at the earlier onset of symptoms [1,2]. Currently, it is established that approximately 10% of PD cases have some genetic involvement [3]. The most common mutations found in Brazilian studies were in PRKN and LRRK2 genes [4]. Understanding the genetic foundation of PD is important for genetic counseling and future genic therapeutics.

Method: We reviewed medical records from EOPD patients (onset between the ages of 21 and 50), followed in a tertiary Movement Disorders (MD) clinic, who had previously undergone genetic testing as part of their clinical assessment using next-generation sequencing technology (NGS) for a panel of 29 PD-associated genes. The diagnosis of PD was made by an MD specialist following the UK Brain Bank criteria. We excluded patients with incomplete data.

Results: Out of 80 patients, 57.5% were male. The mean age of disease onset was 40.3 (21–50) years old. Genetic variants were detected in 38 (47.5%) patients. Pathogenic or likely pathogenic variants were observed in 15 (18.7%) patients. Pathogenic mutations were found in PRKN, GBA, GCH1, LRRK2, and TH. PRKN was the most affected gene with 5 different mutations encountered in 6 individuals, followed by GBA with 4 variants seen in 6 patients. The median age of symptoms onset in patients with PRKN mutations was 5 years earlier than in patients with GBA mutations. Forty different variants of uncertain significance (VUS) were present in 30 (37.5%) participants. Those VUS were identified in 17 of the 29 evaluated genes and LRRK2 was the major stricken gene, with 7 distinct variants found. No difference regarding age was found between patients with and without mutations.

Conclusion: In this study, EOPD patients carried mutations predominantly involving PRKN, GBA, and LRRK2 genes. More studies including Brazilian patients are needed to better understand our genetic landscape. The number of VUS unveiled here reminds us of the large number of mutations we are still unable to clearly define and classify, highlighting this new challenge of incorporating genetic results into clinical practice in days where NGS are readily available.

References: [1] Mehanna R, et al. Age Cutoff for Early-Onset Parkinson’s Disease: Recommendations from the International Parkinson and Movement Disorder Society Task Force on Early Onset Parkinson’s Disease. Mov Disord Clin Pract 2022;9(7):869-878.
[2] Kolicheski A, et al. Early-Onset Parkinson’s Disease: Creating the Right Environment for a Genetic Disorder. J Parkinsons Dis 2022;12(8):2353–2367.
[3] Lunati A, et al. The genetic landscape of Parkinson’s disease. Rev Neurol 2018;174(9):628–643.
[4] Santos-Lobato BL, et al. Genetics of Parkinson’s disease in Brazil: a systematic review of monogenic forms. Arq Neuropsiquiatr 2021;79(7):612-623.

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-profile-of-early-onset-parkinsons-disease-patients-at-a-movement-disorders-center-in-brazil/