{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:18:01Z","timestamp":1786123081884,"version":"build-2736575974"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"<jats:p>\n                    Neurodevelopmental disorders related to protein phosphatase 2 catalytic subunit alpha (\n                    <jats:italic>PPP2CA<\/jats:italic>\n                    ) are currently recognized as Houge\u2013Janssens syndrome 3 (OMIM: 618354), an autosomal dominant disorder characterized by developmental delay, intellectual disability, autism spectrum disorder, seizures, brain abnormalities, and hypotonia. Here, we report a patient with a\n                    <jats:italic>PPP2CA<\/jats:italic>\n                    variant. Trio-based whole-exome sequencing was performed on the patient and her parents, and a novel\n                    <jats:italic>de novo<\/jats:italic>\n                    heterozygous variant\n                    <jats:italic>PPP2CA<\/jats:italic>\n                    (NM_002715: c.218G &amp;gt; A, p.Gly73Asp) was identified, resulting in an amino acid substitution within the catalytic subunit. Clinically, the patient presented with epilepsy, hypotonia, attention-deficit\/hyperactivity disorder, and intact intellectual functioning; there were no structural brain abnormalities.\n                    <jats:italic>PPP2CA<\/jats:italic>\n                    variants are rare, and the variant identified in this study has not been previously reported in the literature or public databases. Our findings support the pathogenicity of this variant and further expand the pathogenic variant spectrum of the\n                    <jats:italic>PPP2CA<\/jats:italic>\n                    gene. Furthermore, the observed genotype\u2013phenotype correlation provides valuable information for prognosis and genetic counseling.\n                  <\/jats:p>","DOI":"10.3389\/fpsyt.2026.1889298","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:44:06Z","timestamp":1786110246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A case report of a novel de novo variant in PPP2CA causing a neurodevelopmental disorder and epilepsy"],"prefix":"10.3389","volume":"17","author":[{"given":"Lei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Dalian Women and Children\u2019s Medical Center","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanfeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Dalian Women and Children\u2019s Medical Center","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guixiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Dalian Women and Children\u2019s Medical Center","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79860","article-title":"B56d-related protein phosphatase 2A dysfunction identified in patients with intellectual disability","volume":"125","author":"Houge","year":"2015","journal-title":"J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201606033","article-title":"A PP2A-B55 recognition signal controls substrate dephosphorylation kinetics during mitotic exit","volume":"214","author":"Cundell","year":"2016","journal-title":"J Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102656","article-title":"Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules","volume":"298","author":"Haanen","year":"2022","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.06.024","article-title":"A conserved motif provides binding specificity to the PP2A-B56 phosphatase","volume":"63","author":"Hertz","year":"2016","journal-title":"Mol Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nature14135","article-title":"Large-scale discovery of novel genetic causes of developmental disorders","volume":"519","year":"2015","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108713","article-title":"The clinical, neuroimaging and molecular characteristics of PPP2R5D related neurodevelopmental disorders: An expanded series with functional characterization and genotype-phenotype analysis","volume":"60","author":"Oyama","year":"2022","journal-title":"J Med Genet"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-025-01901-1","article-title":"Houge-janssens syndrome","volume":"33","author":"Houge","year":"2025","journal-title":"Eur J Hum Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1141804","article-title":"Quantum-based modeling implies that bidentate Arg89-substrate binding enhances serine\/threonine protein phosphatase-2A(PPP2R5D\/PPP2R1A\/PPP2CA)-mediated dephosphorylation","volume":"11","author":"Salter","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1042\/BST20201313","article-title":"Protein phosphatase 2A (PP2A) mutations in brain function, development, and neurologic disease","volume":"49","author":"Verbinnen","year":"2021","journal-title":"Biochem Soc Trans"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1694932","article-title":"PPP2CA knockdown upregulates the expression levels of ferroptosis-related genes TFRC and ACSL4 in colorectal cancer cells by promoting mTOR phosphorylation","volume":"15","author":"Cheng","year":"2025","journal-title":"Front Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.biocel.2017.12.015","article-title":"Protein phosphatase 2AC\u03b1 gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells","volume":"95","author":"Liu","year":"2018","journal-title":"Int J Biochem Cell Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.1059938","article-title":"Clinical and molecular characteristics of a novel rare de novo variant in PPP2CA in a patient with a developmental disorder, autism, and epilepsy","volume":"10","author":"Verbinnen","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.36959\/595\/439","article-title":"A novel PPP2CA gene variant presenting with dystonia and progressive brain atrophy","volume":"6","author":"Cheng","year":"2022","journal-title":"J Pediatr Neurol Neurosci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.002","article-title":"De novo mutations affecting the catalytic C\u03b1 subunit of PP2A, PPP2CA, cause syndromic intellectual disability resembling other PP2A-related neurodevelopmental disorders","volume":"104","author":"Reynhout","year":"2019","journal-title":"Am J Hum Genet"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.01.021","article-title":"Pathogenic de novo variants in PPP2R5C cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum","volume":"112","author":"Verbinnen","year":"2025","journal-title":"Am J Hum Genet"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1889298\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T13:44:07Z","timestamp":1786110247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1889298\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":15,"alternative-id":["10.3389\/fpsyt.2026.1889298"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1889298","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"article-number":"1889298"}}