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Variants in\n                    <jats:italic>CTBP1<\/jats:italic>\n                    have been associated with neurodevelopmental disorder termed HADDTS (Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome; OMIM#617915). However, the pathophysiological mechanism of this genetic disorder remains unclear. Whole exome sequencing was performed on a 20\u2010year\u2010old male patient with severe mental retardation, atrial septal defect, ataxia, and dysmorphic features. The patient was found to have a\n                    <jats:italic>de novo<\/jats:italic>\n                    missense variant, c.107G&gt;C,p.(R36P), within the PLDLS (Pro\u2010Leu\u2010Asp\u2010Leu\u2010Ser) binding cleft of CTBP1. However, the patient did not fulfill the diagnostic criteria for HADDTS. Therefore, the pathophysiological significance of this variant was investigated in\u00a0vitro and in\u00a0vivo, comparing it with p.R342W, a recurrent pathogenic variant in HADDTS. Transient expression of the p.R36P and p.R342W variants reduced the number and total length of dendrites in primary cultured hippocampal neurons. In\u00a0vivo acute expression of them caused a migration delay of excitatory neurons and disrupted both dendritic arborization and spine formation during corticogenesis. Subsequent electrophysiological analyses suggested that these variants reduced excitatory synaptic transmission. Additionally, the p.R36P variant, but not p.R342W, reduced the excitability of layer II\/III pyramidal neurons. We also report two new cases with the p.R342W variant that meet the diagnostic criteria for HADDTS. Our results show that CTBP1 plays an essential role in brain development and that the novel variant may cause a new developmental disorder distinct from HADDTS.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70385-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70385","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T07:11:34Z","timestamp":1770880294000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>CTBP1<\/scp>\n                    In Brain Development: A Novel Variant c.107G&gt;C,p.(R36P) Leads to a Distinct Neurodevelopmental Disorder"],"prefix":"10.1111","volume":"170","author":[{"given":"Takuma","family":"Nishijo","sequence":"first","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research Aichi Developmental Disability Center  Kasugai Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumiko","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurobiology, Institute for Developmental Research Aichi Developmental Disability Center  Kasugai Aichi 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