This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Two agents that have been shown to increase methylation in mice are being used to see if they can produce the same effect in humans, and if increased methylation results in any improvement in Angelman Syndrome. The two drugs that are being tried (folic acid and betaine) are actually vitamin supplements that have a long track record of safety. Used in mega-doses, there is hope that the vitamins will increase methylation without creating side-effects. On the other hand, there is some evidence that folic acid may increase seizures. In addition, the methylation mechanism is not well understood, and it may cause the chromosome to reverse its activity. It is crucial to do a placebo-controlled study to find out whether these medications are beneficial or detrimental to children with Angelman Syndrome.