EFFICACY OF A THERAPEUTIC TREATMENT TRIAL IN ANGELMAN SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 摘要 Angelman综合征(AS)是一种神经学疾病，会导致全球发育迟缓、极少或缺少语言、癫痫发作、不协调步态(共济失调)、睡眠障碍以及其他医疗和行为困难。由于精神障碍不足，以及其他医疗和行为困难所致。AS是由于定位于染色体15q11-q13的编码E6-AP泛素蛋白连接酶(基因符号UBE3A)的母系传播基因缺失所致。本研究旨在评价L-5-甲基四氢叶酸(美他福林)、维生素B12、肌酸和甜菜碱治疗儿童安格曼综合征(AS)的可能疗效。我们认为，饮食干预可能会增加全球DNA甲基化，从而导致父亲染色体甲基化增加，并使用这些饮食干预进一步表达Angelman基因，从而改善这种疾病的症状和医疗问题。 这项研究的所有参与者将包括有文件证明的AS分子诊断的患者。参与者将在0个月、6个月和12个月时在贝勒医学院、圣地亚哥儿童医院、波士顿儿童医院和格林伍德遗传中心接受随访。临床和相关历史数据将在临床访问和检查期间收集，也将通过查阅医疗和实验室记录来收集。入选的受试者将在试验开始和结束时(12个月)接受药物组合和亲自评估。这些信息随后将被输入到符合HIPAA的临床研究数据库中。

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. ABSTRACT Angelman syndrome (AS) is a neurologica disorder that causes global developmental delay, minimal or absent speech, seizures, uncoodinated gait (ataxia), sleep disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of the maternally-transmitted gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. This study has been designed to evaluate the possible therapeutic benefits of L-5-methyltetrahdydrofolate (Metafolin), vitamin B12, creatine and betaine in children with Angelman Syndrome (AS). We believe that dietary manipulation may increase global DNA methylation therefore leading to an increased methylation of the paternal chromosome and further expression of the Angelman gene using these dietary interventions causing an amelioration of the symptoms and medical problems in this disorder. All the participants for the study will include patients who have a documented molecular diagnosis of AS. The participants will be seen at Baylor College of Medicine, Children's Hospital of San Diego, Boston Children's Hospital and the Greenwood Genetics Center at 0 months, 6 months and at 12 months for follow-up. Clinical and relevant historical data will be collected during the clinical visit and examination and also by revieiwing medical and laboratory records. The enrolled subjects will be given the combination of drugs and evaluated in person at the beginning of the trial and at the end (12 months) . This information will then be entered into a HIPAA compliant clinical research database.