{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:48:05Z","timestamp":1790830085004,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"18","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-16-CE12-0005-01 to"],"award-info":[{"award-number":["ANR-16-CE12-0005-01 to"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 EY032976-01"],"award-info":[{"award-number":["R01 EY032976-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background: TASP1 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. Methods: Chromosomal 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. Results: All 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. Conclusion: This 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\u2013Steiner and Kabuki syndrome.<\/jats:p>","DOI":"10.1093\/hmg\/ddac098","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T03:20:21Z","timestamp":1650943221000},"page":"3083-3094","source":"Crossref","is-referenced-by-count":8,"title":["Suleiman-El-Hattab syndrome: a histone modification disorder caused by TASP1 deficiency"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7503-5801","authenticated-orcid":false,"given":"Korbinian M","family":"Riedhammer","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, Klinikum rechts der Isar, School of Medicine, Technical University of Munich , 81675 Munich, Germany"},{"name":"Department of Nephrology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich , 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L","family":"Burgemeister","sequence":"additional","affiliation":[{"name":"Genetikum, Genetic Counseling and Diagnostics , 70173 Stuttgart, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5180-4848","authenticated-orcid":false,"given":"Vincent","family":"Cantagrel","sequence":"additional","affiliation":[{"name":"Developmental Brain Disorders Laboratory, Universit\u00e9 Paris Cit\u00e9 , Imagine Institute, INSERM UMR, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Amiel","sequence":"additional","affiliation":[{"name":"Department of Genetics, AP-HP, Necker Enfants Malades Hospital, Universit\u00e9 Paris Cit\u00e9, Imagine Institute , 75015 Paris, 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