Dystonia-specific mutations in THAP1 alter transcription of genes associated with neurodevelopment and myelin.

ABSTRACT: Dystonia is a neurologic disorder associated with an increasingly large number of genetic variants in many genes, resulting in characteristic disturbances in volitional movement. Dissecting the relationships between these mutations and their functional outcomes is critical in understanding the pathways that drive dystonia pathogenesis. Here we established a pipeline for characterizing an allelic series of dystonia-specific mutations. We used this strategy to investigate the molecular consequences of genetic variation in THAP1, which encodes a transcription factor linked to neural differentiation. Multiple pathogenic mutations associated with dystonia cluster within distinct THAP1 functional domains and are predicted to alter DNA-binding properties and/or protein interactions differently, y

SUBMITTER: Domingo A 

PROVIDER: S-EPMC8595948 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature