Evidence map›Paper›PMID 35512351›Full record

ArticleHuman molecular genetics2022

Suleiman-El-Hattab syndrome: a histone modification disorder caused by TASP1 deficiency.

Korbinian M Riedhammer, Anna L Burgemeister, Vincent Cantagrel, Jeanne Amiel, Karine Siquier-Pernet, Nathalie Boddaert, Jozef Hertecant, Patricia L Kannouche, Caroline Pouvelle, Stephanie Htun and 11 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
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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

21 authors at 12 institutions in 5 countries.

Korbinian M RiedhammerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.ORCID 0000-0002-7503-5801
Anna L BurgemeisterGenetikum, Genetic Counseling and Diagnostics, 70173 Stuttgart, Germany.
Vincent CantagrelDevelopmental Brain Disorders Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR, 75015 Paris, France.ORCID 0000-0002-5180-4848
Jeanne AmielDepartment of Genetics, AP-HP, Necker Enfants Malades Hospital, Université Paris Cité, Imagine Institute, 75015 Paris, France.
Karine Siquier-PernetDevelopmental Brain Disorders Laboratory, Université Paris Cité, Imagine Institute, INSERM UMR, 75015 Paris, France.
Nathalie BoddaertDépartement de radiologie pédiatrique, INSERM UMR 1163 and INSERM U1000, AP-HP, Necker Enfants Malades Hospital, 75015 Paris, France.
Jozef HertecantDivision of Genetics and Metabolics, Department of Pediatrics, Tawam Hospital, Al Ain, United Arab Emirates.
Patricia L KannoucheCNRS UMR 9019, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Gustave Roussy, 94805 Villejuif, France.ORCID 0000-0002-6050-3457
Caroline PouvelleCNRS UMR 9019, Université Paris-Saclay, Equipe labellisée Ligue contre le Cancer, Gustave Roussy, 94805 Villejuif, France.
Stephanie HtunDepartment of Pediatrics, Division of Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
Anne M SlavotinekDepartment of Pediatrics, Division of Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.ORCID 0000-0001-7053-2449
Christian BeetzCentogene GmbH, 18055 Rostock, Germany.
Dan Diego-AlvarezCentogene GmbH, 18055 Rostock, Germany.
Kapil KampeCentogene GmbH, 18055 Rostock, Germany.
Nicole FleischerFDNA Inc., Boston, MA 02111, USA.
Zain AwamlehGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Rosanna WeksbergGenetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.ORCID 0000-0002-6501-4150
Robert KopajtichInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.ORCID 0000-0002-9119-3455
Thomas MeitingerInstitute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, 81675 Munich, Germany.
Jehan SuleimanDivision of Neurology, Department of Pediatrics, Tawam Hospital, Al Ain, United Arab Emirates.ORCID 0000-0003-0914-7650
Ayman W El-HattabDepartment of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.ORCID 0000-0002-5737-5271
Centogene (Germany) · DEInserm · FRTUM Klinikum · DECentre National de la Recherche Scientifique · FRUniversity of California, San Francisco · USGenetikum · DEHospital for Sick Children · CATawam Hospital · AEUnited Arab Emirates University · AEUniversité Paris Cité · FRUniversity of Sharjah · AEUniversity of Toronto · CA

Funding

Genomic analysis of microphthalmia, anophthalmia and colobomaR01EY032976 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI SLAVOTINEK, ANNE M. · 2021 to 2023
$1.3M
NEI NIH HHS R01 EY032976
6 · The paper itself

Abstract

backgroundTASP1 encodes an endopeptidase activating histone methyltransferases of the KMT2 family. Homozygous loss-of-function variants in TASP1 have recently been associated with Suleiman-El-Hattab syndrome. We report six individuals with Suleiman-El-Hattab syndrome and provide functional characterization of this novel histone modification disorder in a multi-omics approach.

methodsChromosomal microarray/exome sequencing in all individuals. Western blotting from fibroblasts in two individuals. RNA sequencing and proteomics from fibroblasts in one individual. Methylome analysis from blood in two individuals. Knock-out of tasp1 orthologue in zebrafish and phenotyping.

resultsAll individuals had biallelic TASP1 loss-of-function variants and a phenotype including developmental delay, multiple congenital anomalies (including cardiovascular and posterior fossa malformations), a distinct facial appearance and happy demeanor. Western blot revealed absence of TASP1. RNA sequencing/proteomics showed HOX gene downregulation (HOXA4, HOXA7, HOXA1 and HOXB2) and dysregulation of transcription factor TFIIA. A distinct methylation profile intermediate between control and Kabuki syndrome (KMT2D) profiles could be produced. Zebrafish tasp1 knock-out revealed smaller head size and abnormal cranial cartilage formation in tasp1 crispants.

conclusionThis work further delineates Suleiman-El-Hattab syndrome, a recognizable neurodevelopmental syndrome. Possible downstream mechanisms of TASP1 deficiency include perturbed HOX gene expression and dysregulated TFIIA complex. Methylation pattern suggests that Suleiman-El-Hattab syndrome can be categorized into the group of histone modification disorders including Wiedemann-Steiner and Kabuki syndrome.

Indexed as

Histone CodeZebrafishAbnormalities, MultipleAnimalsEndopeptidasesFaceHematologic DiseasesHistone MethyltransferasesPhenotypeTranscription Factor TFIIAVestibular DiseasesEndopeptidasesHistone MethyltransferasesTranscription Factor TFIIA

Identifiers

PMID35512351
PMCPMC9476618
OpenAlexW4226296293

What OpenQuestion 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 OpenQuestion graph.