Voor het Angelman Syndroom

pdf Double-Blind Therapeutic Trial in Angelman Syndrome Using Betaine and Folic Acid Populair

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Peters SU 2010 Am J Med Genet 152A-1994.pdf

Angelman syndrome (AS) is caused by reduced or absent expressionof the maternally inherited ubiquitin protein ligase 3A gene(UBE3A), which maps to chromosome 15q11?q13. UBE3A issubject to genomic imprinting in neurons in most regions of thebrain. Expression of UBE3A from the maternal chromosome isessential to prevent AS, because the paternally inherited gene isnot expressed, probably mediated by antisense UBE3A RNA. Wehypothesized that increasing methylation might reduce expressionof the antisense UBE3A RNA, thereby increasing UBE3Aexpression from the paternal gene and ameliorating the clinicalphenotype. We conducted a trial using two dietary supplements,betaine and folic acid to promote global levels of methylationand attempt to activate the paternally inherited UBE3A gene.We performed a number of investigations at regular intervalsincluding general clinical and developmental evaluations, biochemicaldeterminations on blood and urine, and electroencephalographicstudies.Wereport herein the data on 48 children withAS who were enrolled in a double-blind placebo-controlledprotocol using betaine and folic acid for 1 year. There were nostatistically significant changes between treated and untreatedchildren; however, in a small subset of patients we observed somepositive trends.

Peters SU, Bird LM, Kimonis V, Glaze DG,Shinawi LM, Bichell TJ, Barbieri-Welge R,Nespeca M, Anselm I, Waisbren S, Sanborn E,Sun Q, O?Brien WE, Beaudet AL, Bacino CA.2010.

Double-blind therapeutic trial inAngelman syndrome using betaine and folicacid.

Am J Med Genet Part A 152A:1994?2001.