{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:15:33Z","timestamp":1790144133609,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2023,9]]},"abstract":"Abstract<\/jats:title>NAA20 is the catalytic subunit of the NatB complex, which is responsible for N\u2010terminal acetylation of approximately 20% of the human proteome. Recently, pathogenic biallelic variants in NAA20<\/jats:italic> were associated with a novel neurodevelopmental disorder in five individuals with limited clinical information. We report two sisters harboring compound heterozygous variant (c.100C>T (p.Gln34Ter) and c.11T>C p.(Leu4Pro)) in the NAA20<\/jats:italic> gene, identified by exome sequencing. In vitro studies showed that the missense variant p.Leu4Pro resulted in a reduction of NAA20 catalytic activity due to weak coupling with the NatB auxiliary subunit. In addition, unpublished data of the previous families were reported, outlining the core phenotype of the NAA20\u2010related disorder mostly characterized by cognitive impairment, microcephaly, ataxia, brain malformations, dysmorphism and variable occurrence of cardiac defect and epilepsy. Remarkably, our two patients featured epilepsy onset in adolescence suggesting this may be a part of syndrome evolution. Functional studies are needed to better understand the complexity of NAA20<\/jats:italic> variants pathogenesis as well as of other genes linked to N\u2010terminal acetylation.<\/jats:p>","DOI":"10.1111\/cge.14359","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T09:49:36Z","timestamp":1684230576000},"page":"371-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel biallelic variants expand the phenotype of NAA20<\/scp>\u2010related syndrome"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-5919","authenticated-orcid":false,"given":"Gianluca","family":"D'Onofrio","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Universit\u00e0 degli Studi di Genova Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cuccurullo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences Federico II University Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silje Kathrine","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariasavina","family":"Severino","sequence":"additional","affiliation":[{"name":"Neuroradiology Unit IRCCS Istituto Giannina Gaslini Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Radiology Unit of Tortorella Private Hospital Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Br\u00f8nstad","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"AlOwain","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine King Faisal Specialist Hospital and Research Centre (KFSHRC) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Division of Genetics Arnold Palmer Hospital Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia G.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Division of Genetics Arnold Palmer Hospital Orlando Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryn D.","family":"Webb","sequence":"additional","affiliation":[{"name":"School of Medicine and Public Health University of Wisconsin Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Alfalah","sequence":"additional","affiliation":[{"name":"Department of Medical Genomics, Centre for Genomic Medicine King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics \u2013 IRCCS Istituto Giannina Gaslini Genova Italy"},{"name":"Clinical Bioinformatics \u2013 IRCCS Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Uva","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics \u2013 IRCCS Istituto Giannina Gaslini Genova Italy"},{"name":"Clinical Bioinformatics \u2013 IRCCS Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences Federico II University Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Merla","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology University of Naples Federico II Naples Italy"},{"name":"Laboratory of Regulatory and Functional Genomics Fondazione IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo (Foggia) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo Damiano","family":"Salpietro","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Applied Sciences University of L'Aquila Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Universit\u00e0 degli Studi di Genova Genoa Italy"},{"name":"Unit of Medical Genetics \u2013 IRCCS Istituto Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Striano","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Universit\u00e0 degli Studi di Genova Genoa Italy"},{"name":"Pediatric Neurology and Muscular Diseases Unit IRCCS Istituto \u201cGiannina Gaslini\u201d Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Accogli","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Specialized Medicine McGill University Health Centre Montreal Quebec Canada"},{"name":"Department of Human Genetics, Faculty of Medicine McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3005-147X","authenticated-orcid":false,"given":"Thomas","family":"Arnesen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Bergen Bergen Norway"},{"name":"Department of Biological Sciences University of Bergen Bergen Norway"},{"name":"Department of Surgery Haukeland University Hospital Bergen Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonilda","family":"Bilo","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences Federico II University Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.02.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901931106"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.01.053"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20080658"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210303109"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010021\u201001264\u20100"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.08.016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.57491"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.09.010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010021\u201002427\u20104"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316966"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz111"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.03.004"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23001"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu611"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.2028611"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3116\u201012.2012"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.755267"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2008.332"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14359","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T12:59:53Z","timestamp":1692277193000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,16]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/cge.14359"],"URL":"https:\/\/doi.org\/10.1111\/cge.14359","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,16]]},"assertion":[{"value":"2023-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}