20.500.12556/RUL-185147 Enrichment of rare variants in nuclear-encoded mitochondrial metabolism genes in patients with early-onset or familial parkinson’s disease Introduction: Parkinson’s disease (PD) is a prevalent neurodegenerative disorder, with several proposed pathogenic mechanisms. Given the established role of mitochondrial dysfunction in PD, this study seeks to investigate the enrichment of rare genetic variants tied to mitochondrial metabolism in cases of early-onset and familial PD. Methods: We performed a retrospective analysis on 248 early-onset and familial PD patients and 1622 control individuals. We assessed both pathway-level and gene-level burden of germline rare variants detected using exome sequencing in 467 nuclear genes related to mitochondrial metabolism. Results: Gene-set mutation burden analysis indicated an increased burden in genes associated with mtDNA maintenance. In addition, gene-level analysis identified a possible association between PD and rare variant burden in 14 mitochondrial metabolism-related genes under dominant or recessive inheritance models. Conclusions: Our findings support a potential contribution of rare germline variants affecting mitochondrial metabolism to the susceptibility in early-onset and familial PD. mitochondrial metabolism mitochondrial variants mutation burden analysis true false true Angleški jezik Ni določen Članek v reviji 2026-07-24 11:26:47 2026-07-24 11:26:48 2026-08-06 07:55:33 0000-00-00 00:00:00 2026 0 0 8 str. iss. 4 Vol. 17 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.858 2073-4425 10.3390/genes17040472 276781571 RAZ_Bergant_Gaber_2026.pdf RAZ_Bergant_Gaber_2026.pdf 1 52A1AA7FA42386FCBFBACD180A53BE1D fa4a8a5e842b59587be113364690a4711a7d5695bee64f749ac2dd3ad4f66a50 d4e690f3-8741-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=243368 https://www.mdpi.com/2073-4425/17/4/472 1 8d8b9d8b-8741-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=243366 Fakulteta za računalništvo in informatiko Medicinska fakulteta 0 0 0