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Double‐blind therapeutic trial in Angelman syndrome using betaine and folic acid
Author(s) -
Peters Sarika U.,
Bird Lynne M.,
Kimonis Virginia,
Glaze Daniel G.,
Shinawi Lina M.,
Bichell Terry Jo,
BarbieriWelge Rene,
Nespeca Mark,
Anselm Irina,
Waisbren Susan,
Sanborn Erica,
Sun Qin,
O'Brien William E.,
Beaudet Arthur L.,
Bacino Carlos A.
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33509
Subject(s) - ube3a , angelman syndrome , genomic imprinting , betaine , x inactivation , biology , methylation , genetics , ubiquitin ligase , dna methylation , imprinting (psychology) , antisense rna , gene , folic acid , gene expression , medicine , ubiquitin , x chromosome , biochemistry
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. © 2010 Wiley‐Liss, Inc.