Identification of PSMB5 as a genetic modifier of fragile X-associated tremor/ataxia syndrome.

ABSTRACT: Fragile X–associated tremor/ataxia syndrome (FXTAS) is a debilitating late-onset neurodegenerative disease in premutation carriers of the expanded CGG repeat in FMR1 that presents with a spectrum of neurological manifestations, such as gait ataxia, intention tremor, and parkinsonism [P. J. Hagerman, R. J. Hagerman, Ann. N. Y. Acad. Sci. 1338, 58–70 (2015); S. Jacquemont et al., JAMA 291, 460–469 (2004)]. Here, we performed whole-genome sequencing (WGS) on male premutation carriers (CGG55–200) and prioritized candidate variants to screen for candidate genetic modifiers using a Drosophila model of FXTAS. We found 18 genes that genetically modulate CGG-associated neurotoxicity in Drosophila, such as Prosbeta5 (PSMB5), pAbp (PABPC1L), e(y)1 (TAF9), and CG14231 (OSGEPL1). Among them, knockdown

SUBMITTER: Kong HE 

PROVIDER: S-EPMC9295734 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature