Evidence map›Paper›PMID 38592547›Full record

ArticleHuman genetics2024

Loss-of-function variants affecting the STAGA complex component SUPT7L cause a developmental disorder with generalized lipodystrophy.

Johannes Kopp, Leonard A Koch, Hristiana Lyubenova, Oliver Küchler, Manuel Holtgrewe, Andranik Ivanov, Christele Dubourg, Erika Launay, Sebastian Brachs, Stefan Mundlos and 5 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Human genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Identification of biallelic loss-of-functionJournal of medical genetics · 2026
    Article
  3. Article
  4. 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

15 authors.

Johannes KoppInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-0391-1497
Leonard A KochInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0003-4943-198X
Hristiana LyubenovaInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-5590-3835
Oliver KüchlerInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0009-0008-2628-2890
Manuel HoltgreweCore Unit Bioinformatics (CUBI), Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-3051-1763
Andranik IvanovCore Unit Bioinformatics (CUBI), Berlin Institute of Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-4824-1925
Christele DubourgService de Génétique Moléculaire et Génomique, CHU, Rennes, F-35033, France.ORCID http://orcid.org/0000-0003-1345-4522
Erika LaunayService de Cytogénétique et Biologie cellulaire, Hôpital Pontchaillou - CHU Rennes, 2 rue Henri Le Guilloux - Rennes cedex 9, France, Rennes, F-35033, France.ORCID http://orcid.org/0000-0003-1546-7319
Sebastian BrachsDepartment of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.ORCID http://orcid.org/0000-0002-6336-3939
Stefan MundlosInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-9788-3166
Nadja EhmkeInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0003-1449-9909
Dominik SeelowInstitute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-9746-4412
Mélanie FradinService de Génétique Clinique, Centre Référence Déficiences Intellectuelles CRDI, Hôpital Sud - CHU Rennes, 16 boulevard de Bulgarie - BP 90347, Rennes cedex 2, Rennes, F-35203, France.ORCID http://orcid.org/0000-0002-2535-2198
Uwe Kornak *Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany.ORCID http://orcid.org/0000-0002-4582-9838
Björn Fischer-Zirnsak *Institute of Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt Universität zu Berlin, 13353, Berlin, Germany. bjoern.fischer@charite.de.ORCID http://orcid.org/0000-0002-1075-7571

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Generalized lipodystrophy is a feature of various hereditary disorders, often leading to a progeroid appearance. In the present study we identified a missense and a frameshift variant in a compound heterozygous state in SUPT7L in a boy with intrauterine growth retardation, generalized lipodystrophy, and additional progeroid features. SUPT7L encodes a component of the transcriptional coactivator complex STAGA. By transcriptome sequencing, we showed the predicted missense variant to cause aberrant splicing, leading to exon truncation and thereby to a complete absence of SUPT7L in dermal fibroblasts. In addition, we found altered expression of genes encoding DNA repair pathway components. This pathway was further investigated and an increased rate of DNA damage was detected in proband-derived fibroblasts and genome-edited HeLa cells. Finally, we performed transient overexpression of wildtype SUPT7L in both cellular systems, which normalizes the number of DNA damage events. Our findings suggest SUPT7L as a novel disease gene and underline the link between genome instability and progeroid phenotypes.

Indexed as

Fetal Growth RetardationLipodystrophy, Congenital GeneralizedTranscription FactorsDNA DamageDNA RepairFibroblastsHeLa CellsHumansLipodystrophyLoss of Function MutationMaleMutation, MissenseSUPT7L protein, humanTranscription FactorsAberrant splicingLipodystrophyProgeroid disorderSTAGA complexSUPT7LWiedemann-Rautenstrauch syndrome

Identifiers

PMID38592547
PMCPMC11098864

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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.