Emerging role of a systems biology approach to elucidate factors of reduced penetrance: transcriptional changes in THAP1-linked dystonia as an example.
Med Genet
; 34(2): 131-141, 2022 Jun.
Article
in En
| MEDLINE
| ID: mdl-38835919
ABSTRACT
Pathogenic variants in THAP1 can cause dystonia with a penetrance of about 50 %. The underlying mechanisms are unknown and can be considered as means of endogenous disease protection. Since THAP1 encodes a transcription factor, drivers of this variability putatively act at the transcriptome level. Several transcriptome studies tried to elucidate THAP1 function in diverse cellular and mouse models, including mutation carrier-derived cells and iPSC-derived neurons, unveiling various differentially expressed genes and affected pathways. These include nervous system development, dopamine signalling, myelination, or cell-cell adhesion. A network diffusion analysis revealed mRNA splicing, mitochondria, DNA repair, and metabolism as significant pathways that may represent potential targets for therapeutic interventions.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Med Genet
Year:
2022
Document type:
Article
Affiliation country:
Germany
Country of publication:
Germany