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. 2016 Sep 28;7(10):77. doi: 10.3390/genes7100077

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© 2016 by the authors; licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

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Model for timing and nature of fragile X mental retardation 1 (FMR1) hypermethylation in Fragile X syndrome (FXS) human embryonic stem cells (hESCs). Abnormal methylation is first achieved on full expansions in FXS at a restricted time point before/during embryo implantation. Once established, it is irreversible and is clonally maintained. CGG expansions that escape abnormal methylation during this limited time frame remain unmethylated or become further inactivated by a second wave of de novo methylation later during differentiation. Mostly methylated (mosiacism) means that some of the cells are methylated and that some are not.