Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
Am J Med Genet A. 2010 Aug;152A(8):1994-2001. doi: 10.1002/ajmg.a.33509.
Angelman syndrome (AS) is caused by reduced or absent expression of the maternally inherited ubiquitin protein ligase 3A gene (UBE3A), which maps to chromosome 15q11-q13. UBE3A is subject to genomic imprinting in neurons in most regions of the brain. Expression of UBE3A from the maternal chromosome is essential to prevent AS, because the paternally inherited gene is not expressed, probably mediated by antisense UBE3A RNA. We hypothesized that increasing methylation might reduce expression of the antisense UBE3A RNA, thereby increasing UBE3A expression from the paternal gene and ameliorating the clinical phenotype. We conducted a trial using two dietary supplements, betaine and folic acid to promote global levels of methylation and attempt to activate the paternally inherited UBE3A gene. We performed a number of investigations at regular intervals including general clinical and developmental evaluations, biochemical determinations on blood and urine, and electroencephalographic studies. We report herein the data on 48 children with AS who were enrolled in a double-blind placebo-controlled protocol using betaine and folic acid for 1 year. There were no statistically significant changes between treated and untreated children; however, in a small subset of patients we observed some positive trends.
天使综合征（AS）是由母系遗传的泛素蛋白连接酶 3A 基因（UBE3A）表达减少或缺失引起的，该基因定位于 15q11-q13 染色体上。UBE3A 在大脑大多数区域的神经元中受到基因组印迹的调控。UBE3A 从母系染色体的表达对于预防 AS 至关重要，因为父系遗传的基因不表达，可能是由反义 UBE3A RNA 介导的。我们假设增加甲基化可能会降低反义 UBE3A RNA 的表达，从而增加来自父系基因的 UBE3A 表达，并改善临床表型。我们进行了一项使用两种膳食补充剂（甜菜碱和叶酸）来促进整体甲基化水平并尝试激活父系遗传的 UBE3A 基因的试验。我们定期进行了多项研究，包括一般临床和发育评估、血液和尿液的生化测定以及脑电图研究。我们在此报告了 48 名接受 AS 治疗的儿童的数据，他们参加了一项为期 1 年的双盲安慰剂对照研究，使用甜菜碱和叶酸治疗。治疗组和未治疗组之间没有统计学上的显著差异；然而，在一小部分患者中，我们观察到一些积极的趋势。
