Evidence map›Paper›PMID 29304373›Full record

ArticleAmerican journal of human genetics2018

Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes.

Erfan Aref-Eshghi, David I Rodenhiser, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, Rebecca L Hood, Dennis E Bulman, Kristin D Kernohan and 5 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
112citing papers in PubMed, 1 pooled it
9.5field-weighted citation impact, top 1% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

112 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.

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  11. Identification of an episignature for the MEF2C-associated syndrome.European journal of human genetics : EJHG · 2026
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52 more citing papers are in PubMed but not listed here.

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

15 authors at 5 institutions in 2 countries.

Erfan Aref-EshghiDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON N6A5W9, Canada.
David I RodenhiserDepartments of Pediatrics, Biochemistry and Oncology, Western University and Children's Health Research Institute, London, ON N6A5C1, Canada.
Laila C SchenkelDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada.
Hanxin LinDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON N6A5W9, Canada.
Cindy SkinnerGreenwood Genetics Center, Greenwood, SC 29646, USA.
Peter AinsworthDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON N6A5W9, Canada.
Guillaume ParéDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S4L8, Canada.
Rebecca L HoodDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H8M5, Canada.
Dennis E BulmanChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H5B2, Canada.
Kristin D KernohanChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H5B2, Canada.
Care4Rare Canada Consortium
Kym M BoycottChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H5B2, Canada.
Philippe M CampeauDepartment of Pediatrics, University of Montreal, Montreal, QC H3T1J4, Canada.
Charles SchwartzGreenwood Genetics Center, Greenwood, SC 29646, USA.
Bekim SadikovicDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON N6A5W9, Canada. Electronic address: bekim.sadikovic@lhsc.on.ca.
Western University · CAUniversity of Ottawa · CAGreenwood Genetic Center · USMcMaster University · CAUniversité de Montréal · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. In the present study, we examined peripheral blood samples from a large cohort of individuals encompassing 14 Mendelian disorders displaying mutations in the genes encoding proteins of the epigenetic machinery. We demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these epi-signatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, we have demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and we highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery.

Indexed as

Genome, Human5' Untranslated RegionsCase-Control StudiesChildChild, PreschoolCohort StudiesDemographyDNA MethylationEpigenesis, GeneticHumansModels, GeneticMutationNeurodevelopmental DisordersProbabilityReproducibility of ResultsYoung Adult5' Untranslated RegionsATRX syndromeCHARGE syndromeClaes-Jensen syndromeepigenomic machineryFloating Harbor syndromeKabuki syndromemachine learningmolecular diagnosispediatric developmental disordersSotos syndrome

Identifiers

PMID29304373
PMCPMC5777983
OpenAlexW2782149093

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.