{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:18Z","timestamp":1792790418372,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,28]]},"group-title":"Genetic and Genomic Medicine","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke","award":["K02NS140483"],"award-info":[{"award-number":["K02NS140483"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>CBX1<\/jats:italic>\n                  -related syndrome is characterized by developmental delay, hypotonia, autistic features, and mild dysmorphic features. This syndrome is caused by heterozygous missense variants in\n                  <jats:italic>CBX1<\/jats:italic>\n                  , which encodes heterochromatin protein 1 beta (HP1\u03b2). These variants are situated within the chromodomain of HP1\u03b2, a critical region that mediates the interaction between HP1\u03b2 and trimethylated H3K9. While a prior study identified three individuals with pathogenic\n                  <jats:italic>CBX1<\/jats:italic>\n                  variants, the variant and clinical spectrum of\n                  <jats:italic>CBX1<\/jats:italic>\n                  -related syndrome remains largely unknown. Here we report three patients with novel\n                  <jats:italic>de novo<\/jats:italic>\n                  heterozygous variants in\n                  <jats:italic>CBX1<\/jats:italic>\n                  . Patients with\n                  <jats:italic>CBX1<\/jats:italic>\n                  p.(Leu40Pro) and p.(Cys60Arg) manifested with global developmental delay, while the patient with\n                  <jats:italic>CBX1<\/jats:italic>\n                  p.(Cys60Gly) primarily exhibited speech delay without concurrent motor developmental delay. All variants reside within chromodomain of the HP1\u03b2 protein. Interestingly,\n                  <jats:italic>in vitro<\/jats:italic>\n                  cellular assays revealed that\n                  <jats:italic>CBX1<\/jats:italic>\n                  p.(Cys60Gly) variant showed an intermediate cellular phenotype between the wild type and the\n                  <jats:italic>CBX1<\/jats:italic>\n                  p.(Leu40Pro) and p.(Cys60Arg) variants, suggesting a possible genotype-phenotype correlation. This report provides further evidence that missense variants within the chromodomain of HP1\u03b2 cause a syndromic neurodevelopmental disorder,\n                  <jats:italic>CBX1<\/jats:italic>\n                  -related syndrome.\n                <\/jats:p>","DOI":"10.64898\/2026.09.28.26363820","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:50:10Z","timestamp":1790635810000},"source":"Crossref","is-referenced-by-count":0,"title":["Expanding clinical and variant spectrum of\n                  <i>CBX1<\/i>\n                  -related syndrome: Report of three novel cases"],"prefix":"10.64898","author":[{"given":"Graciela","family":"Carrillo","sequence":"first","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Fujino","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harrison","family":"Higgs","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Kabahizi","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy","family":"Le","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Rabin","sequence":"additional","affiliation":[{"name":"Clinical Genetic Services, New York University Grossman School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Pappas","sequence":"additional","affiliation":[{"name":"Clinical Genetic Services, New York University Grossman School of Medicine, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Crunk","sequence":"additional","affiliation":[{"name":"GeneDx, LLC, Gaithersburg, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara","family":"Ranguin","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Guadeloupe University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Mortreux","sequence":"additional","affiliation":[{"name":"GCS AURAGEN, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"AURAGEN consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn","family":"Lackmy","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Guadeloupe University Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A","family":"Gadia","sequence":"additional","affiliation":[{"name":"Nicklaus Children\u2019s Hospital, Miami, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew Hoi Kin","family":"Chau","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China"},{"name":"The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill A.","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA"},{"name":"Baylor Genetics, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-7480","authenticated-orcid":false,"given":"Kosuke","family":"Izumi","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, University of Texas Southwestern Medical Center and Children\u2019s Medical Center Dallas, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100103001028000_2026.09.28.26363820v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2023.100861"},{"key":"2026100103001028000_2026.09.28.26363820v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/35065138"},{"key":"2026100103001028000_2026.09.28.26363820v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature722"},{"key":"2026100103001028000_2026.09.28.26363820v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/35065132"},{"key":"2026100103001028000_2026.09.28.26363820v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"2026100103001028000_2026.09.28.26363820v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-020-02246-z"},{"key":"2026100103001028000_2026.09.28.26363820v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.22.4673"},{"key":"2026100103001028000_2026.09.28.26363820v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3229"},{"key":"2026100103001028000_2026.09.28.26363820v1.9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030241"},{"key":"2026100103001028000_2026.09.28.26363820v1.10","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzl007"},{"key":"2026100103001028000_2026.09.28.26363820v1.11","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5240"},{"key":"2026100103001028000_2026.09.28.26363820v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00218-0"},{"key":"2026100103001028000_2026.09.28.26363820v1.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0153-8"},{"key":"2026100103001028000_2026.09.28.26363820v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2026100103001028000_2026.09.28.26363820v1.15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz457"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.28.26363820","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:00:23Z","timestamp":1790848823000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.09.28.26363820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":15,"URL":"https:\/\/doi.org\/10.64898\/2026.09.28.26363820","relation":{},"subject":[],"published":{"date-parts":[[2026,9,28]]},"subtype":"preprint"}}