Evidence map›Paper›PMID 31640736›Full record

ArticleOrphanet journal of rare diseases2019

A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome.

Julia Han, Terry Jo Bichell, Stephanie Golden, Irina Anselm, Susan Waisbren, Carlos A Bacino, Sarika U Peters, Lynne M Bird, Virginia Kimonis

Registry-linked trialOpen access · goldAbstract readControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00348933 (Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
0.2field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00348933 nacompletednot on this map

Efficacy of a Therapeutic Treatment Trial in Angelman Syndrome

TypeinterventionalSponsorUniversity of California, San DiegoRan2006 to 2010Enrolled90ConditionsAngelman Syndrome, Nervous System DiseasesArmsBetaine, Creatine, Metafolin, Vitamin B12
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it, 5 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 1 country.

Julia HanDivision of Genetics and Genomic Medicine, Department of Pediatrics, University of California at Irvine, 101 The City Drive South, Orange, CA, 92868, USA.
Terry Jo BichellConsortium for Outcome Measures and Biomarkers for Neurodevelopmental Disorders, Nashville, TN, USA.
Stephanie GoldenDivision of Genetics and Metabolism, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Irina AnselmDepartment of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Susan WaisbrenDivision of Genetics and Metabolism, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Carlos A BacinoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Sarika U PetersDepartment of Pediatrics, Vanderbilt University, Vanderbilt Kennedy Center for Research on Human Development, Nashville, TN, USA.
Lynne M BirdDepartment of Pediatrics, University of California, San Diego, CA, USA.
Virginia KimonisDivision of Genetics and Genomic Medicine, Department of Pediatrics, University of California at Irvine, 101 The City Drive South, Orange, CA, 92868, USA. vkimonis@uci.edu.ORCID 0000-0003-1567-4449
Boston Children's Hospital · USUniversity of California, Irvine · USBaylor College of Medicine · USNeuroDevelopment Center · USUniversity of California San Diego · USVanderbilt University · US

Funding

University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1M
RARE DISEASE CRC FOR NEW THERAPIES AND NEW DIAGNOSTICSU54RR019478 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI BEAUDET, ARTHUR L. · 2003 to 2008
$7.3M
Research Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1M
NCATS NIH HHS UL1 TR001414NICHD NIH HHS U54 HD083211NIH HHS U54 RR019478
6 · The paper itself

Abstract

backgroundAngelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele. Consequently, only the maternally inherited UBE3A gene is expressed in mature neurons. AS occurs due to deletions of the maternal 15q11 - 13 region, paternal uniparental disomy (UPD), imprinting center defects, mutations in the maternal UBE3A gene, or other unknown genetic malfunctions that result in a silenced maternal UBE3A gene in the specific imprinted regions of the brain.

resultsA potential treatment strategy for AS is to increase methylation of UBE3A-ATS to promote expression of the paternal UBE3A gene and thus ameliorate the clinical phenotypes of AS. We treated two sets of male identical twins with class I deletions with a 1 year treatment trial of either betaine and folic acid versus placebo. We found no statistically significant changes in the clinical parameters tested at the end of the 1 year trial, nor did we find any significant adverse events.

conclusionsThis study tested the hypothesis that by increasing the methylation of the UBE3A-antisense transcript in Angelman syndrome to promote expression of the silenced paternal UBE3A gene we may ameliorate the clinical phenotypes of AS. We treated two sets of identical twins with placebo versus betaine and folic acid. Although this study represented a novel approach to treating Angelman syndrome, the differences in the developmental testing results was not significant. This paper also discusses the value of monozygotic twin studies in minimizing confounding variables and its utility in conducting small treatment studies.

trial registrationNCT00348933 . Registered 6 July 2006.

Indexed as

Angelman SyndromeBetaineChildDouble-Blind MethodFolic AcidGastrointestinal AgentsHumansMaleSequence DeletionTwins, MonozygoticVitamin B ComplexBetaineFolic AcidGastrointestinal AgentsVitamin B ComplexAngelman syndromeBetaineDeletionFolic acidMethylationMethyl donorsSilencing

Identifiers

PMID31640736
PMCPMC6806546
OpenAlexW2981924232

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.