{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:41:17Z","timestamp":1792464077237,"version":"4.5.0"},"reference-count":10,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>T\u2010complex protein 1<\/jats:italic>\n                    (\n                    <jats:italic>TCP1<\/jats:italic>\n                    ) encodes the TCP1\u03b1 subunit, one of eight subunits of the chaperonin containing TCP1 ring complex (TRiC). Heterozygous\n                    <jats:italic>TCP1<\/jats:italic>\n                    variants cause autosomal dominant neurodevelopmental disorder characterized by developmental delay or intellectual disability, seizures, pyramidal or cerebellar signs, and brain malformations, particularly polymicrogyria. However, the reported clinical spectrum remains limited. We report a 4\u2010year\u2010old girl with global developmental delay, speech and motor delay, behavioral dysregulation, microcephaly, hypotonia with core weakness, and a previously unreported heterozygous likely pathogenic\n                    <jats:italic>TCP1<\/jats:italic>\n                    variant, c.1392delT (p.A465Qfs*3). This frameshift variant is located in exon 11, truncates the final 16.5% of the protein, is predicted to undergo nonsense\u2010mediated decay, and is absent from gnomAD. Biological parental testing was unavailable, precluding determination of variant inheritance. Brain magnetic resonance imaging (MRI) demonstrated an absent septum pellucidum with mild bilateral frontal sulcation\/gyration asymmetry without polymicrogyria; the optic nerves and pituitary were normal. No seizures were documented through age 4\u2009years. Additional findings included bicuspid aortic valve with mild aortic insufficiency, asthma, severe eczema\/atopy, and multiple food allergies. This case suggests that the molecular and neuroimaging spectrum of\n                    <jats:italic>TCP1<\/jats:italic>\n                    \u2010related neurodevelopmental disorder may be broader than previously recognized; however, a causal association between\n                    <jats:italic>TCP1<\/jats:italic>\n                    and absent septum pellucidum cannot be established from a single case. The relationship of the cardiac and atopic findings to\n                    <jats:italic>TCP1<\/jats:italic>\n                    remains uncertain. Additional cases and functional studies are needed to clarify genotype\u2013phenotype relationships.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70335","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:34:55Z","timestamp":1792463695000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Absent Septum Pellucidum Without Polymicrogyria or Seizures in\n                    <scp>TCP1<\/scp>\n                    \u2010Related Neurodevelopmental Disorder"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4610-0415","authenticated-orcid":false,"given":"David","family":"Biton","sequence":"first","affiliation":[{"name":"Department of Pediatrics State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8537-2515","authenticated-orcid":false,"given":"Dibyendu","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Medicine (Division of Hematology and Oncology) State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3980-4981","authenticated-orcid":false,"given":"Ria","family":"Garg","sequence":"additional","affiliation":[{"name":"Center of Development, Behavior, and Genetics State University of New York Upstate Medical University  Syracuse New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"4770","DOI":"10.1016\/j.cell.2022.11.014","article-title":"Structural Visualization of the Tubulin Folding Pathway Directed by Human Chaperonin TRiC\/CCT","volume":"185","author":"Gestaut D.","year":"2022","journal-title":"Cell"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1146\/annurev-genet-112414-054639","article-title":"Nonsense\u2010Mediated mRNA Decay: Degradation of Defective Transcripts Is Only Part of the Story","volume":"49","author":"He F.","year":"2015","journal-title":"Annual Review of Genetics"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1126\/science.adp8721","article-title":"Brain Malformations and Seizures by Impaired Chaperonin Function of TRiC","volume":"386","author":"Kraft F.","year":"2024","journal-title":"Science"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.str.2012.03.007","article-title":"The Molecular Architecture of the Eukaryotic Chaperonin TRiC\/CCT","volume":"20","author":"Leitner A.","year":"2012","journal-title":"Structure"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.pediatrneurol.2022.07.011","article-title":"Isolated Absent Septum Pellucidum: A Retrospective Study of Fetal Diagnosis and Postnatal Outcomes","volume":"136","author":"Pickup E. E. S.","year":"2022","journal-title":"Pediatric Neurology"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/emboj\/18.1.85","article-title":"In Vivo Newly Translated Polypeptides Are Sequestered in a Protected Folding Environment","volume":"18","author":"Thulasiraman V.","year":"1999","journal-title":"EMBO Journal"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pediatrneurol.2024.12.014","article-title":"Prenatally Diagnosed Absent Septum Pellucidum and Septo\u2010Optic Dysplasia: A Narrative Review and Practical Recommendations for Pediatric Neurologists","volume":"164","author":"Venkatesan C.","year":"2025","journal-title":"Pediatric Neurology"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ejhg.2009.125","article-title":"Septo\u2010Optic Dysplasia","volume":"18","author":"Webb E. A.","year":"2010","journal-title":"European Journal of Human Genetics"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/358245a0","article-title":"TCP1 Complex Is a Molecular Chaperone in Tubulin Biogenesis","volume":"358","author":"Yaffe M. B.","year":"1992","journal-title":"Nature"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1038\/nsmb.1515","article-title":"Defining the TRiC\/CCT Interactome Links Chaperonin Function to Stabilization of Newly Made Proteins With Complex Topologies","volume":"15","author":"Yam A. Y.","year":"2008","journal-title":"Nature Structural & Molecular Biology"}],"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.70335","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70335","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70335","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T02:34:58Z","timestamp":1792463698000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,19]]},"references-count":10,"alternative-id":["10.1002\/ajmg.a.70335"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70335","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,19]]},"assertion":[{"value":"2026-08-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70335"}}