Evidence map›Paper›PMID 41010044›Full record

ArticleGenes2025

De Novo Variants Predominate in Autism Spectrum Disorder.

Richard G Boles, Omri Bar, Philip T Boles, Zoë R Hill, Richard E Frye

Abstract read
In one paragraph

Article in Genes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. A De NovoInternational journal of molecular sciences · 2026
    Article
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

5 authors.

Richard G BolesMitochondrial & Molecular Medicine, Pasadena, CA 91108, USA.
Omri BarMitochondrial & Molecular Medicine, Pasadena, CA 91108, USA.
Philip T BolesMitochondrial & Molecular Medicine, Pasadena, CA 91108, USA.
Zoë R HillAutism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA.
Richard E FryeAutism Discovery and Treatment Foundation, Phoenix, AZ 85050, USA.ORCID 0000-0003-4442-2937

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutism spectrum disorder (ASD) is a common condition with substantial personal and financial burdens of lifelong implication. Multiple twin studies have confirmed a genetic or inherited component at ~80%, higher than any other common condition. However, ASD's rapidly accelerating prevalence, now at 1 in 31 in the USA, appears to defy a predominantly genetic basis and implicate our rapidly changing environment. A potential explanation for this paradox is a recent increase in de novo variants (DNVs), which are "new" mutations present in the patient yet absent in both parents. The present authors recently reported using trio whole-genome sequencing (trio-WGS) that DNVs highly likely to be highly disease-associated ("Principal Diagnostic Variants", PDVs), mostly missense variants, were present in (25/50) 50% of the ASD patients clinically evaluated by our team.

methodsThe current study was designed to support this observation with trio-WGS in 100 additional unrelated ASD patients.

resultsDe novo PDVs were identified in 47/100 (47%) of cases, in close approximation to our previous work. Using non-transcribed (up and downstream) variants for all genes as a control group, these DNV-PDVs were far more likely (

conclusionsOur proposed model for ASD, with prominent DNVs in most that are genetic yet not inherited, predicts the known predominant genetic pathogenesis and the accelerating prevalence of ASD, possibly from environmental factors, including insufficient nutrients and toxicant exposures, and/or the disrupted folate metabolism known to be associated with ASD. Limitations to this study include predominant inclusion of severely affected individuals and the lack of an unaffected control group and functional validation of variant pathogenicity.

Indexed as

Autism Spectrum DisorderGenetic Predisposition to DiseaseChildChild, PreschoolFemaleGenetic VariationHumansMaleMutationMutation, MissenseWhole Genome Sequencingautismdiagnostic yielddisease modelDNA sequencingmissensepolygenic inheritancesilent variantssynonymous variantswhole genome sequencing

Identifiers

PMID41010044
PMCPMC12470000

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.