Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner
Abstract
:1. Introduction
2. Results
2.1. GAA Repeat Tract Interruptions Can Be Detected through Alteration of TP PCR Electropherograms
2.2. Interruption at the 3′ End of the GAA Repeat Tract Is Associated with a Shorter GAA1 Repeat Size and a Later Age at Onset
2.3. Modelling the Impact of Interruptions by Subgrouping
3. Discussion
4. Materials and Methods
4.1. Patient Cohort and Ethical Statement
4.2. Triplet Repeat Primed PCR (TP PCR)
4.3. Assessing and Modelling the Impact of Interruptions
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Lacking 5′ and 3′ Interruption (n = 29) | 5′ Interruption (n = 19) | 3′ Interruption (n = 32) | 5′ and 3′ Interruption (n = 21) | |
---|---|---|---|---|
Age at Onset (years) | 10 (7–14.0) | 16 (10–25) | 20 (13–30) | 16 (7–28) |
Number of FXN GAA repeats | ||||
Shorter Allele (GAA1) | 782 (656–960) | 683 (483–765) | 552 (316–758) | 696 (349–827) |
Longer Allele (GAA2) | 1000 (842–1144) | 1040 (800–1100) | 974 (765–1040) | 900 (783–1301) |
24.5 | 22.9 | 48.1 | 25.3 | |
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Nethisinghe, S.; Kesavan, M.; Ging, H.; Labrum, R.; Polke, J.M.; Islam, S.; Garcia-Moreno, H.; Callaghan, M.F.; Cavalcanti, F.; Pook, M.A.; et al. Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner. Int. J. Mol. Sci. 2021, 22, 7507. https://doi.org/10.3390/ijms22147507
Nethisinghe S, Kesavan M, Ging H, Labrum R, Polke JM, Islam S, Garcia-Moreno H, Callaghan MF, Cavalcanti F, Pook MA, et al. Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner. International Journal of Molecular Sciences. 2021; 22(14):7507. https://doi.org/10.3390/ijms22147507
Chicago/Turabian StyleNethisinghe, Suran, Maheswaran Kesavan, Heather Ging, Robyn Labrum, James M. Polke, Saiful Islam, Hector Garcia-Moreno, Martina F. Callaghan, Francesca Cavalcanti, Mark A. Pook, and et al. 2021. "Interruptions of the FXN GAA Repeat Tract Delay the Age at Onset of Friedreich’s Ataxia in a Location Dependent Manner" International Journal of Molecular Sciences 22, no. 14: 7507. https://doi.org/10.3390/ijms22147507