Evidence map›Paper›PMID 41214838›Full record

ArticleClinical epigenetics2025

A frameshift variant in activity-dependent neuroprotective protein (ADNP) causes nucleocytoskeletal alterations in a dizygotic male twin: a case study.

Claudio Peter D'Incal, Anke Van Dijck, Dale John Annear, Lusine Harutyunyan, Ellen Elinck, Alexander J M Dingemans, Bert B A de Vries, Ligia Mateiu, Marije Meuwissen, Anna C Jansen and 1 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

11 authors.

Claudio Peter D'IncalCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Anke Van DijckFamily Medicine and Population Health (FAMPOP), Department of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Dale John AnnearCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Lusine HarutyunyanFamily Medicine and Population Health (FAMPOP), Department of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
Ellen ElinckCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Alexander J M DingemansDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Bert B A de VriesDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Ligia MateiuCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Marije MeuwissenCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Anna C JansenTranslational Neurosciences, University of Antwerp, Antwerp, Belgium. Anna.Jansen@uza.be.
R Frank KooyCognitive Genetics (COGNET), Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium. frank.kooy@uantwerpen.be.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe Helsmoortel-Van der Aa syndrome is an autosomal-dominant neurodevelopment disorder caused by heterozygous de novo variants in the Activity-Dependent Neuroprotective Protein (ADNP) gene, characterized by autism, intellectual disability, dysmorphic facial features, and deficits in multiple organ systems. ADNP is a zinc finger DNA-binding protein that primarily interacts with chromatin remodelers regulating embryonic development, while also associating with components of the cytoskeleton, thereby regulating autophagy and microtubule dynamics during development. In this study, we investigated these nucleocytoskeletal alterations explaining neurodevelopmental delay in a child with Helsmoortel-Van der Aa syndrome who had an unaffected dizygotic twin brother.

resultsWe performed a genome-wide methylation array on PBMCs from dizygotic twins, showing a predominant CpG hypomethylation episignature. Enrichment analysis of methylated genes revealed significant pathway changes in actin filament organization, Wnt signaling, embryonic development, heart development, and the immune system. In addition, transcriptome sequencing substantiated the affected pathways regulating nuclear and cytoskeletal filamentous alterations associated with autism and neurodevelopmental delay. Brain magnetic resonance imaging showed a mild generalized prominence of the subarachnoid space overlying both hemispheres, revealing intricate patterns of neurodevelopmental delay.

conclusionsWe report the first molecular study performed on dizygotic twins of which one was diagnosed with Helsmoortel-Van der Aa syndrome, revealing Wnt signaling and filamentous cytoskeletal alterations as a potential drug targets for therapy. LIMITATIONS: Indications for neurodegeneration, following these cytoskeletal perturbations, have been observed in cellular and murine models for the Helsmoortel-Van der Aa syndrome. However, clinical evidence remains unclear due to the young age of patients, limiting long-term studies on the aging brain. Further longitudinal imaging studies combined with histopathological autopsy sections are required to study the impact of an ADNP variant in the brain as patients come to age.

Indexed as

Nerve Tissue ProteinsAutistic DisorderChildChild, PreschoolDNA MethylationHomeodomain ProteinsHumansMagnetic Resonance ImagingMaleTwins, DizygoticADNP protein, humanHomeodomain ProteinsNerve Tissue ProteinsActivity-dependent neuroprotective proteinHelsmoortel-Van der Aa syndromeNeurodevelopmentNucleocytoskeletal abnormalitiesTwins

Identifiers

PMID41214838
PMCPMC12599069

What Socratic holds

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Registered trials

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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.