{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:46:50Z","timestamp":1791892010464,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K02NS140483"],"award-info":[{"award-number":["K02NS140483"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>CBX1<\/jats:italic>\n                    \u2010related 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                    \u2010related syndrome remain 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 the chromodomain of the HP1\u03b2 protein. Interestingly, in\u00a0vitro cellular assays revealed that the\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\u2013phenotype 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                    \u2010related syndrome.\n                  <\/jats:p>","DOI":"10.1111\/cge.70262","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:50:47Z","timestamp":1791888647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding Clinical and Variant Spectrum of\n                    <scp>\n                      <i>CBX1<\/i>\n                    <\/scp>\n                    \u2010Related Syndrome: Report of Three Novel Cases"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4050-7834","authenticated-orcid":false,"given":"Graciela","family":"Carrillo","sequence":"first","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics University of Texas Southwestern Medical Center and Children's Medical Center Dallas  Dallas Texas 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's Medical Center Dallas  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0317-0122","authenticated-orcid":false,"given":"Harrison","family":"Higgs","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics University of Texas Southwestern Medical Center and Children's Medical Center Dallas  Dallas Texas 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's Medical Center Dallas  Dallas Texas 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's Medical Center Dallas  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4906-7428","authenticated-orcid":false,"given":"Rachel","family":"Rabin","sequence":"additional","affiliation":[{"name":"Clinical Genetic Services New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5625-2598","authenticated-orcid":false,"given":"John","family":"Pappas","sequence":"additional","affiliation":[{"name":"Clinical Genetic Services New York University Grossman School of Medicine  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2027-3818","authenticated-orcid":false,"given":"Amy","family":"Crunk","sequence":"additional","affiliation":[{"name":"GeneDx, LLC  Gaithersburg Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-8090","authenticated-orcid":false,"given":"Kara","family":"Ranguin","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Guadeloupe University Hospital  Guadeloupe France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2914-1961","authenticated-orcid":false,"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  Guadeloupe France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3016-8037","authenticated-orcid":false,"given":"Carlos A.","family":"Gadia","sequence":"additional","affiliation":[{"name":"Nicklaus Children's Hospital  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0945-1938","authenticated-orcid":false,"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\u2010Baylor College of Medicine Joint Center for Medical Genetics  Hong Kong SAR 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