Objective: To characterize the genetic and phenotypic profile of Argentinean Parkinson’s patients and contribute to the understanding of the genetic heterogeneity of this disease.

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder. Its aetiology is multifactorial and results from the interaction of genetic and environmental factors. Therefore, it is essential to know the genotype of PD patients from different populations, especially those underrepresented in previous studies.

Method: A genotype/phenotype analysis was performed on a cohort of Argentinean patients enrolled in the international LARGE-PD consortium. Although 136 patients with a clinical diagnosis of PD were included, the present analysis of PD-associated gene variant occurrence and phenotype includes the first 46 patients whose results have been received to date. Variants present in ClinVar were classified according to ACMG guidelines.

Results: Variants were detected in 18 individuals/46 (39.1%). Five out of 46 patients (5/46- 10.9%) had a pathogenic variant (ClinVar). Pathogenic LRRK2 variants were identified in 2/46 patients (4.4%), 2/46 patients (4.4%) had pathogenic GBA1 variants and 1 of 46 patients (2.2%) had a pathogenic PRKN variant. 

The subgroup of patients with LRRK2 mutations showed an earlier onset compared to the other variants and with tremor as the first motor symptom.

Conclusion: This study represents the first report of an Argentinean cohort with genotype/phenotype characterisation in PD. In our cohort, the prevalence of pathogenic variants was 10.87%, a finding consistent with the existing literature. The results obtained provide valuable information on the genetic heterogeneity of the disease and highlight the importance of genetic diagnosis for a better understanding of PD pathogenesis and the development of personalised therapeutic strategies. Future research with larger cohorts and functional analysis of the identified variants will allow us to expand our knowledge of the genetics of PD in Argentina and its interaction with local or regional environmental factors.

genes

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MDS Abstracts - https://www.mdsabstracts.org/abstract/description-genotype-phenotype-of-patients-with-parkinsons-disease-report-of-an-argentinean-cohort-included-in-the-large-pd-consortium/