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Variants in the\n                  <jats:italic>CSMD1-3<\/jats:italic>\n                  paralogs were GWAS-associated with cognition, attention-deficit hyperactivity disorder (ADHD), schizophrenia and brain structure, suggesting that these genes could be linked to neurodevelopmental disorders (NDD). Indeed, rare biallelic variants in all three\n                  <jats:italic>CSMD<\/jats:italic>\n                  paralogs were recently associated with epilepsy, while rare biallelic variants in\n                  <jats:italic>CSMD1<\/jats:italic>\n                  were also linked with intellectual disability and cortical malformations. We identified nine individuals from eight families carrying\n                  <jats:italic>CSMD2<\/jats:italic>\n                  biallelic missense variants in developmental delay\/intellectual disability cohorts. Affected individuals presented with autism spectrum disorder (ASD), ADHD and brain anomalies. Consistent with gnomAD metrics that suggest\n                  <jats:italic>CSMD2<\/jats:italic>\n                  haploinsufficiency, we also report two families segregating monoallelic\n                  <jats:italic>CSMD2<\/jats:italic>\n                  frameshift variants, which complement a described\n                  <jats:italic>de novo<\/jats:italic>\n                  truncation variant in an ASD proband. We concomitantly report two phenotypically overlapping individuals with\n                  <jats:italic>de novo CSMD2<\/jats:italic>\n                  missense variants and compare them to twelve\n                  <jats:italic>de novo CSMD2<\/jats:italic>\n                  cases identified in published trio analyses. UK Biobank analyses showed nominally significant enrichment of ADHD, ASD and neuroticism in volunteers carrying at least one rare\n                  <jats:italic>CSMD2<\/jats:italic>\n                  variant.\n                  <jats:italic>In silico<\/jats:italic>\n                  modelling and immunofluorescence assays showed that mutated residues in affected individuals with biallelic and\n                  <jats:italic>de novo<\/jats:italic>\n                  missense variants are clustering in two regions and that the encoded proteins showed impaired membrane localization and an increased cytoplasmic aggregation.\n                <\/jats:p>\n                <jats:p>\n                  Zebrafish crispant larvae for the orthologous\n                  <jats:italic>csmd2<\/jats:italic>\n                  presented with microcephaly, smaller cerebellum, and reduced Purkinje cell size. Larvae also displayed decreased swimming velocity, diminished connectivity between the optic tecta, and abnormal peripheral neuronal branching.\n                <\/jats:p>\n                <jats:p>\n                  We demonstrate that rare, likely pathogenic variants in\n                  <jats:italic>CSMD2<\/jats:italic>\n                  are associated with both autosomal recessive and dominant forms of NDD further substantiating the functional significance of CSMD paralogs in neurogenesis\/synapse formation.\n                <\/jats:p>","DOI":"10.64898\/2026.09.24.26361611","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:25:11Z","timestamp":1790796311000},"source":"Crossref","is-referenced-by-count":0,"title":["Haploinsufficiency,\n                  <i>de novo<\/i>\n                  and biallelic missense variants in\n                  <i>CSMD2<\/i>\n                  are associated with neurodevelopmental disorders"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8552-4319","authenticated-orcid":false,"given":"Clara","family":"Pailler-Pradeau","sequence":"first","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne Victoria","family":"Lem\u00e9e","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire, Department of Translational Medicine and Neurogenetics, Universit\u00e9 de Strasbourg, CNRS, Inserm, IGBMC UMR 7104-UMR-S 1258, F-67404 Illkirch, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6708-091X","authenticated-orcid":false,"given":"Caterina","family":"Cevallos","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland"},{"name":"Swiss Institute of Bioinformatics, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Mattioli","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Chrast","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sissy","family":"Bassani","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Darvish","sequence":"additional","affiliation":[{"name":"Nikagene Genetic Diagnostic Laboratory, Gorgan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginevra","family":"Zanni","sequence":"additional","affiliation":[{"name":"Unit of Rare Disorders and Medical Genetics, Bambino Ges\u00fa Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna Stefania","family":"Colafati","sequence":"additional","affiliation":[{"name":"Oncological Neuroradiology and Advanced Imaging Unit, Bambino Ges\u00fa Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Travaglini","sequence":"additional","affiliation":[{"name":"Lab of Medical Genetics, Bambino Ges\u00fa Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5612-821X","authenticated-orcid":false,"given":"Francesco","family":"Nicita","sequence":"additional","affiliation":[{"name":"Unit of Muscular and 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W , Nazir S , Anilkumar AC , Shaban K . Attention Deficit Hyperactivity Disorder. In: StatPearls. StatPearls Publishing; 2023. 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