{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:12:17Z","timestamp":1787987537278,"version":"build-2784847793"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"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":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Biallelic variants in\n                    <jats:italic>PUS3<\/jats:italic>\n                    have recently been recognized as a rare cause of neurodevelopmental disorders. Pseudouridine synthase\u20103 encoded by\n                    <jats:italic>PUS3<\/jats:italic>\n                    is an enzyme important for modification of various RNAs, including transfer RNA (tRNA). Here we present the clinical and genetic features of 21 individuals with biallelic\n                    <jats:italic>PUS3<\/jats:italic>\n                    variants: seven new and 14 previously reported individuals, where clinical features of two were updated. The clinical and genetic information were collected through collaborations or by literature search. All individuals were characterized by the local clinicians and the gene variants were identified by next generation sequencing (NGS) based methodologies. The clinical picture was dominated by global developmental delay, epilepsy, hypotonia and microcephaly. Gray sclera, which has previously been suggested to be a characteristic feature of\n                    <jats:italic>PUS3<\/jats:italic>\n                    \u2010associated phenotypes, was reported in only seven individuals. The patients had some dysmorphic facial features, but a recognizable gestalt was not observed. In conclusion, homozygous and compound heterozygous\n                    <jats:italic>PUS3<\/jats:italic>\n                    variants lead to a rare neurodevelopmental disorder. Further functional studies are necessary to understand involvement of PUS3 and tRNA biogenesis in normal and abnormal brain development.\n                  <\/jats:p>","DOI":"10.1111\/cge.14051","type":"journal-article","created":{"date-parts":[[2021,8,20]],"date-time":"2021-08-20T05:27:40Z","timestamp":1629437260000},"page":"628-633","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Clinical and molecular delineation of\n                    <scp>\n                      <i>PUS3<\/i>\n                    <\/scp>\n                    \u2010associated neurodevelopmental disorders"],"prefix":"10.1111","volume":"100","author":[{"given":"Miriam","family":"N\u00f8stvik","sequence":"first","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Kateta","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0088-0792","authenticated-orcid":false,"given":"Bitten","family":"Sch\u00f6newolf\u2010Greulich","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Afenjar","sequence":"additional","affiliation":[{"name":"APHP. Sorbonne Universit\u00e9, Centre de R\u00e9f\u00e9rence Malformations et maladies cong\u00e9nitales du cervelet et d\u00e9ficiences intellectuelles de causes rares d\u00e9partement de g\u00e9n\u00e9tique et embryologie m\u00e9dicale, H\u00f4pital Trousseau  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magalie","family":"Barth","sequence":"additional","affiliation":[{"name":"Centre Hospitalo\u2010Universitaire d\u2019Angers D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-9290","authenticated-orcid":false,"given":"Felix","family":"Boschann","sequence":"additional","affiliation":[{"name":"Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Institute of Medical Genetics and Human Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Doummar","sequence":"additional","affiliation":[{"name":"APHP. Sorbonne Universit\u00e9, Centre de R\u00e9f\u00e9rence Malformations et maladies cong\u00e9nitales du cervelet et d\u00e9ficiences intellectuelles de causes rares, service de neurop\u00e9diatrie H\u00f4pital Trousseau  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Centre for Rare Diseases University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Keren","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re AP\u2010HP.Sorbonne universit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila A.","family":"Livshits","sequence":"additional","affiliation":[{"name":"D\u00e9partement de g\u00e9n\u00e9tique, H\u00f4pital Piti\u00e9\u2010Salp\u00eatri\u00e8re AP\u2010HP.Sorbonne universit\u00e9  Paris France"},{"name":"Institute of Molecular Biology and Genetics National Academy of Science of Ukraine  Kyiv Ukraine"},{"name":"State Institution \u201cInstitute of Pediatrics, Obstetrics and Gynecology named after Academician O.M. Lukyanova, National Academy of Medical Sciences of Ukraine\u201d  Kyiv Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mei","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's Hospital, Member of ERN Epicare University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohyun","family":"Park","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Pisano","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's Hospital, Member of ERN Epicare University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clement","family":"Prouteau","sequence":"additional","affiliation":[{"name":"Centre Hospitalo\u2010Universitaire d\u2019Angers D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Umair","sequence":"additional","affiliation":[{"name":"Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC) King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs (MNGH)  Riyadh Saudi Arabia"},{"name":"Department of Life Sciences, School of Science University of Management and Technology (UMT)  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Waqas","sequence":"additional","affiliation":[{"name":"Department of Zoology, Division of Science and Technology University of Education  Lahore Punjab Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-3561","authenticated-orcid":false,"given":"Alban","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Centre Hospitalo\u2010Universitaire d\u2019Angers D\u00e9partement de G\u00e9n\u00e9tique M\u00e9dicale  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzo","family":"Guerrini","sequence":"additional","affiliation":[{"name":"Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's Hospital, Member of ERN Epicare University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke S.","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"Department of Regional Health Research University of Southern Denmark  Odense Denmark"},{"name":"The Danish Epilepsy Centre  Dianalund Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4777-5802","authenticated-orcid":false,"given":"Zeynep","family":"T\u00fcmer","sequence":"additional","affiliation":[{"name":"Kennedy Center, Department of Clinical Genetics Copenhagen University Hospital  Copenhagen Denmark"},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/15476286.2014.992278"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1316"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203456200"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi001109m"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.048173.114"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/152165400410182"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-083118-015334"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-016-1665-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13443"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.07.019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.04.002"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000306"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-019-04049-1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13720"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.7124\/bc.0008D6"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23935"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199935710.001.0001"},{"key":"e_1_2_8_19_1","unstructured":"Genome Aggregation Database (GnomAD v.2.1.1). PUS3 2021.https:\/\/gnomad.broadinstitute.org\/gene\/ENSG00000110060?dataset=gnomad_r2_1."},{"key":"e_1_2_8_20_1","unstructured":"SpliceAI Lookup Broad Institute.https:\/\/spliceailookup.broadinstitute.org. Accessed July 11 2021."},{"key":"e_1_2_8_21_1","unstructured":"HGVS (Human Genome Variation Society).https:\/\/varnomen.hgvs.org\/."},{"key":"e_1_2_8_22_1","unstructured":"VariantValidator.https:\/\/variantvalidator.org\/."},{"key":"e_1_2_8_23_1","unstructured":"Genetic Variant Interpretation Tool University of Maryland School of Medicine.https:\/\/www.medschool.umaryland.edu\/genetic_variant_interpretation_tool1.html\/."},{"key":"e_1_2_8_24_1","unstructured":"OMIM.org. Pseudouridylate Synthase 3 2021.https:\/\/www.omim.org\/entry\/616283?search=PUS3&highlight=pus3#5."}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14051","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.14051","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.14051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:26:57Z","timestamp":1741735617000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.14051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/cge.14051"],"URL":"https:\/\/doi.org\/10.1111\/cge.14051","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.14051\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.14051\/v1\/review2","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"2021-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}