{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T14:22:04Z","timestamp":1747146124709,"version":"3.40.5"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterozygous pathogenic variants in <jats:italic>PPP2R5D<\/jats:italic> gene are associated with <jats:italic>PPP2R5D<\/jats:italic>\u2010related neurodevelopmental disorder, a rare autosomal dominant condition, characterized by neurodevelopmental impairment in childhood, macrocephaly\/megalencephaly, hypotonia, epilepsy, and dysmorphic features. Up\u2010to\u2010date, only approximately 100 cases have been published in the literature and the full phenotypic and genotypic spectrum have not yet been fully described. <jats:italic>PPP2R5D<\/jats:italic> gene encodes the B56\u03b4 subunit of the PP2A enzyme complex. We describe a neonatal form of <jats:italic>PPP2R5D<\/jats:italic>\u2010related disorder with early infantile death, caused by a novel in\u2010frame deletion causing loss of 8 amino acids and insertion of serine at position 201 (p.Phe194_Pro201delinsSer) of the B56\u03b4 subunit. This deletion is predicted to disrupt a critical acidic loop of amino acids important for binding other subunits of the PP2A enzyme complex, and harbors many of the residues previously reported to cause a mild\u2013moderate form of this condition. This report describes a neonatal lethal presentation of the <jats:italic>PPP2R5D<\/jats:italic>\u2010related neurodevelopmental disorder and provides additional evidence that disruption of the acidic loop is an important pathomechanism underlying <jats:italic>PPP2R5D<\/jats:italic>\u2010related disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.63307","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T07:20:37Z","timestamp":1685431237000},"page":"2416-2421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An in\u2010frame deletion affecting the critical acid loop of <scp><i>PPP2R5D<\/i><\/scp> is associated with a neonatal lethal form of <scp><i>PPP2R5D<\/i><\/scp>\u2010related neurodevelopmental disorder"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1982-1349","authenticated-orcid":false,"given":"Ghadd","family":"Alhajaj","sequence":"first","affiliation":[{"name":"Department of Pediatrics Unaizah College of Medicine and Medical Sciences, Qassim University  Saudi Arabia"},{"name":"Department of Pediatrics, Division of Pediatric Neurology McGill University Health Center  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Lacroix","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology McGill University Health Center  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yannis","family":"Trakadis","sequence":"additional","affiliation":[{"name":"Department of Specialized Medicine, Division of Medical Genetics McGill University Health Center  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jarred","family":"Garfinkle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology McGill University Health Center  Montreal Quebec Canada"},{"name":"Research Institute of the McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myriam","family":"Srour","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Neurology McGill University Health Center  Montreal Quebec Canada"},{"name":"Research Institute of the McGill University Health Centre  Montreal Quebec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041286"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14135"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011071"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011189"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2020.104123"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79860"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25863"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv182"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1733984"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-021-00287-1"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.36.22081"},{"key":"e_1_2_10_14_1","unstructured":"Mirzaa G. Foss K. Nattakom M. &Chung W. K.(2019).PPP2R5D\u2010related neurodevelopmental disorder. GeneReviews\u00ae[Internet]."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62241"},{"key":"e_1_2_10_16_1","article-title":"Clinical, neuroimaging and molecular characteristics of PPP2R5D\u2010related neurodevelopmental disorders: An expanded series with functional characterisation and genotype\u2013phenotype analysis","volume":"60","author":"Oyama N.","year":"2022","journal-title":"Journal of Medical Genetics"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.05.001"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.02.036"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0466-9"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1100"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20201313"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25943"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky427"},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2021\/6661860","article-title":"A novel missense variant in the gene PPP2R5D causes a rare neurodevelopmental disorder with increased phenotype","volume":"2021","author":"Yan L.","year":"2021","journal-title":"BioMed Research International"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-017-0182-4"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T07:46:24Z","timestamp":1692690384000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,30]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1002\/ajmg.a.63307"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63307","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2023,5,30]]},"assertion":[{"value":"2023-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}