As future hiPSC-based studies include a growing number of patients with rare CGRs, they are likely to include individuals with mar elements; we recommend that the precise structure of novel CGRs be clarified by karyotyping before moving forward with hiPSC-based studies. Our work suggests that although mar elements can be maintained with relative stability in mosaic proliferating HF populations, they are frequently lost during the reprogramming process. More critically, the extent of mosaicism in patient HFs and hiPSCs is not particularly predictive of the extent of mosaicism present in patient-derived NPCs. While the generation of spontaneous isogenic carrier and non-carrier hiPSCs from the same patients is fortuitous, the difficulty resolving carrier status in individual living cells makes these hiPSCs a difficult platform for molecular and cellular phenotyping in disease-modeling studies.
