PRKN variants identified in Turkish cohort with suspected hereditary Parkinson disease
Investigators evaluated 36 patients with clinically suspected hereditary Parkinson disease using targeted next-generation sequencing, multiplex ligation-dependent probe amplification, and Sanger sequencing. Clinically relevant PRKN variants were detected in five patients, including homozygous pathogenic mutations in three individuals and compound heterozygous deletions in one. Additional variants of uncertain significance were identified in seven patients across multiple Parkinson-associated genes. The findings demonstrate the utility of combining NGS and copy-number analysis for molecular diagnosis and provide population-specific mutational data for genetic counseling in Turkey.
The original study
Genetic findings in a Turkish clinical cohort with hereditary Parkinson's disease.
- Authors
- Ozata Aksoy D, Tunca Y, Sonkaya AR, Torun D, Korucu O
- Journal
- Neurogenetics
- Type
- Journal Article
- PMID
- 42836888
Original abstract
PURPOSE: Parkinson's disease (PD) is a multifactorial neurodegenerative disorder driven by a complex interplay of genetic and environmental factors. This study aimed to characterize the mutational spectrum in a cohort of patients with clinically suspected hereditary PD using complementary genetic testing approaches. MATERIALS AND METHODS: A total of 36 patients underwent genetic evaluation. Targeted next-generation sequencing (NGS) of a 10-gene PD panel was performed in 35 patients, Multiplex ligation-dependent probe amplification (MLPA)-based copy-number analysis using an 8-gene panel was conducted in 9 patients, and targeted Sanger sequencing was performed in one patient with a known familial PRKN variant. RESULTS: The most clinically relevant findings involved the PRKN gene. A homozygous pathogenic variant in the PRKN gene was detected in 3 patients, compound heterozygous deletions involving the PRKN and PACRG genes in one patient, and a single heterozygous PRKN variant classified as pathogenic was detected in one patient. Additionally, variants of uncertain significance were identified in 7 patients in the ATP13A2, PRKN, VPS35, PINK1, and PLA2G6 genes. CONCLUSION: Using complementary molecular genetic techniques, we identified clinically relevant genetic findings in a cohort of 36 patients with suspected hereditary Parkinson's disease. These findings provide population-specific data on the mutational spectrum of PD in a Turkish clinical cohort and contribute to the characterization of the regional genetic landscape.