In the variegated silencing model in PBMCs, the proportion of spared cells decreases with increasing GAA-TR length until it plateaus at 500 triplets, at which the maximum of both number of silenced cells and severity of FXN deficiency has been reached. If such an effect occurs in affected tissues in patients, there should be a similar ceiling effect of GAA-TR length on clinical severity. Patients with GAA-TR levels greater than this ceiling would constitute a subpopulation with relatively similar frataxin levels and potentially more homogeneous clinical features when controlling for disease duration and age. Based on the variegated silencing model described in PBMCs, we aimed to determine whether the clinical features of FRDA reach a similar ceiling in which severity of symptoms reaches a maximum and worsens minimally past a certain GAA-TR length.
Saturday, May 28, 2022
Clinical Evidence for Variegated Silencing in Patients With Friedreich Ataxia
Layne N. Rodden, Christian Rummey, Yi Na Dong, David R. Lynch; Neurol Genet Jun 2022, 8 (3) e683; DOI: 10.1212/NXG.0000000000000683
