Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease
Abstract
:1. Introduction
2. Cis-Acting Genetic Modifiers
3. Trans-Acting Genetic Modifiers: DNA Mismatch Repair Pathway Genes
Genes | Effect |
---|---|
FAN1 | FAN1 depletion in animal models and humans accelerates repeat expansion [48]. Increased expression promotes CAG repeat stability and is associated with delayed disease onset [49,50,55]. Variants that delay or hasten disease onset [10,53]. |
MLH1 | The MLH1 gene is associated with brain CAG instability in Htt knock-in mice [61]. MLH1 delays disease onset [59]. |
MSH3 | Promotes somatic CAG expansions, thus contributing to an earlier onset [62,63,64]. Variants are implicated in disease progression [11]. |
PMS1, PMS2, LIG1 | Variants alter disease onset [12]. |
4. Somatic Mutations and Mosaicism
5. RNA-Related Pathology
6. Mitochondrial Mutations
7. Epigenetics
8. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Pengo, M.; Squitieri, F. Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease. Genes 2024, 15, 807. https://doi.org/10.3390/genes15060807
Pengo M, Squitieri F. Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease. Genes. 2024; 15(6):807. https://doi.org/10.3390/genes15060807
Chicago/Turabian StylePengo, Marta, and Ferdinando Squitieri. 2024. "Beyond CAG Repeats: The Multifaceted Role of Genetics in Huntington Disease" Genes 15, no. 6: 807. https://doi.org/10.3390/genes15060807