Genetic architecture of a single cohort of 230 Indian Parkinson's Disease patients

• Published in: Parkinsonism & related disorders 2024-12, Vol.129, p.107157, Article 107157
• Main Authors: Kamath, Sneha D., Phulpagar, Prashant, Holla, Vikram V., Kamble, Nitish, Yadav, Ravi, Muthusamy, Babylakshmi, Kumar Pal, Pramod
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Aged; Cross-Sectional Studies; Dystonia - genetics; Exome Sequencing; Female; Genetics; Glucosylceramidase - genetics; Group VI Phospholipases A2 - genetics; Humans; India; Male; Middle Aged; PARK-GBA1; PARK-PLA2G6; PARK-PRKN; Parkinson disease; Parkinson Disease - genetics; Retrospective Studies
• ISSN: 1353-8020; 1873-5126; 1873-5126
• DOI: 10.1016/j.parkreldis.2024.107157

Indian Parkinson's Disease (PD) patients are severely underrepresented in terms of genetic studies and little is known about the frequency of variants and their impact on motor and nonmotor symptoms (NMS). This retrospective cross-sectional study was conducted in PD patients undergoing treatment at a tertiary care hospital from India. Patients were advised genetic testing if they had (i) age at onset (AAO) of motor symptoms at or before 50 years (EOPD), (ii) positive family history of PD, parkinsonism or dystonia. All patients underwent whole exome sequencing and potentially pathogenic variants were identified. Clinical and genetic data were available for 230 (163 males, 70.4 %) patients. Thirty-five pathogenic and likely pathogenic variants in various PD genes were identified in 47 patients resulting in a yield of 20.4 %. In the remaining, 82 patients had either variants of uncertain significance or had variants in genes not associated with parkinsonism and 101 patients did not have any non-benign variants. Patients with genetically mediated PD had a lower AAO and statistically greater frequency of dystonia (36.2 %), postural instability (29.8 %) and mood disorder (29.8 %) and a higher Hoehn and Yahr score (2.9). Among the 47 patients, 11 patients had PARK-PRKN, six patients had PARK-PLA2G6, and 22 patients had PARK-GBA1. Around one-fifth of early-onset PD can have an underlying monogenetic cause. PARK-GBA1, PARK-PRKN and PARK-PLA2G6 are the commoner causes of genetically mediated PD in India. Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia. •This study reflects the spectrum of genetic aetiology in patients of Parkinson disease presenting to a tertiary care centre.•Around one-fifth of early-onset PD can have an underlying genetic cause.•PARK-GBA1, PARK-PRKN and PARK-PLA2G6 are the commoner causes of genetically mediated PD in India.•Patients with genetic cause had an earlier age at onset, and more frequent dystonia, postural instability and dyskinesia.