Evidence map›Paper›PMID 38498291›Full record

ArticleNeurogenetics2024

DYT-THAP1: exploring gene expression in fibroblasts for potential biomarker discovery.

Sokhna Haissatou Diaw, Sylvie Delcambre, Christoph Much, Fabian Ott, Vladimir S Kostic, Agata Gajos, Alexander Münchau, Simone Zittel, Hauke Busch, Anne Grünewald and 2 more

Abstract read
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In one paragraph

Article in Neurogenetics, 2024. 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
0.3field-weighted citation impact, top 49% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

12 authors at 5 institutions in 4 countries.

Sokhna Haissatou DiawInstitute of Neurogenetics, University of Lübeck, 23562, Lübeck, Germany.
Sylvie DelcambreLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, L-4362, Luxembourg.
Christoph MuchInstitute of Neurogenetics, University of Lübeck, 23562, Lübeck, Germany.
Fabian OttInstitute of Experimental Dermatology and Institute of Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.
Vladimir S KosticInstitute of Neurology, School of Medicine, University of Belgrade, Belgrade, 11000, Serbia.
Agata GajosDepartment of Extrapyramidal Diseases, Medical University of Lodz, Lodz, 90-647, Poland.
Alexander MünchauInstitute of Systems Motor Science, University of Lübeck, 23562, Lübeck, Germany.
Simone ZittelDepartment of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Hauke BuschInstitute of Experimental Dermatology and Institute of Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.
Anne GrünewaldLuxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, L-4362, Luxembourg.
Christine KleinInstitute of Neurogenetics, University of Lübeck, 23562, Lübeck, Germany.
Katja LohmannInstitute of Neurogenetics, University of Lübeck, 23562, Lübeck, Germany. katja.lohmann@uni-luebeck.de.ORCID http://orcid.org/0000-0002-5121-1460
University of Lübeck · DEUniversity of Luxembourg · LUMedical University of Lodz · PLUniversität Hamburg · DEUniversity of Belgrade · RS

Funding

Deutsche Forschungsgemeinschaft FOR2488Deutsche Forschungsgemeinschaft LO1555/9-2Luxembourgish Research Fund INTER/DFG/19/14429377
6 · The paper itself

Abstract

Dystonia due to pathogenic variants in the THAP1 gene (DYT-THAP1) shows variable expressivity and reduced penetrance of ~ 50%. Since THAP1 encodes a transcription factor, modifiers influencing this variability likely operate at the gene expression level. This study aimed to assess the transferability of differentially expressed genes (DEGs) in neuronal cells related to pathogenic variants in the THAP1 gene, which were previously identified by transcriptome analyses. For this, we performed quantitative (qPCR) and Digital PCR (dPCR) in cultured fibroblasts. RNA was extracted from THAP1 manifesting (MMCs) and non-manifesting mutation carriers (NMCs) as well as from healthy controls. The expression profiles of ten of 14 known neuronal DEGs demonstrated differences in fibroblasts between these three groups. This included transcription factors and targets (ATF4, CLN3, EIF2A, RRM1, YY1), genes involved in G protein-coupled receptor signaling (BDKRB2, LPAR1), and a gene linked to apoptosis and DNA replication/repair (CRADD), which all showed higher expression levels in MMCs and NMCs than in controls. Moreover, the analysis of genes linked to neurological disorders (STXBP1, TOR1A) unveiled differences in expression patterns between MMCs and controls. Notably, the genes CUEDC2, DRD4, ECH1, and SIX2 were not statistically significantly differentially expressed in fibroblast cultures. With > 70% of the tested genes being DEGs also in fibroblasts, fibroblasts seem to be a suitable model for DYT-THAP1 research despite some restrictions. Furthermore, at least some of these DEGs may potentially also serve as biomarkers of DYT-THAP1 and influence its penetrance and expressivity.

Indexed as

Apoptosis Regulatory ProteinsBiomarkersDNA-Binding ProteinsFibroblastsAdultCells, CulturedDystoniaFemaleGene ExpressionGene Expression ProfilingHumansMaleMiddle AgedMutationNuclear ProteinsTranscriptomeApoptosis Regulatory ProteinsBiomarkersDNA-Binding ProteinsNuclear ProteinsTHAP1 protein, humanDystoniaExpressionFibroblastsqPCRTHAP1

Identifiers

PMID38498291
OpenAlexW4392917569

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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 OpenQuestion graph.