A pathogenic variant in RAB32 causes autosomal dominant Parkinson's disease and activates LRRK2 kinase.

ABSTRACT:

Background

Parkinson's disease (PD) is a progressive neurodegenerative disorder. Mendelian forms have revealed multiple genes, with a notable emphasis on membrane trafficking; RAB GTPases play an important role in PD as a subset are both regulators and substrates of LRRK2 protein kinase. To explore the role of RAB GTPases in PD, we undertook a comprehensive examination of their genetic variability in familial PD.

Methods

Affected probands from 130 multi-incident PD families underwent whole-exome sequencing and genotyping, Potential pathogenic variants in 61 RAB GTPases were genotyped in relatives to assess disease segregation. These variants were also genotyped in a larger case-control series, totaling 3,078 individuals (2,734 with PD). The single most significant finding wa

SUBMITTER: Gustavsson EK 

PROVIDER: S-EPMC10827257 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature