{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T08:04:47Z","timestamp":1753862687439,"version":"3.41.2"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>Chiari malformation type 1 (CMI) is defined by the herniation of cerebellar tonsils of 5\u2009mm or more, with possible neurological consequences, including compression of the neural tissue and\/or anomalies in cerebral spinal fluid circulation. The etiology of CMI is not fully elucidated, with both genetic and environmental factors being involved. Several genes and pathways involved in bone development are pointed out like genes of the WNT, FGF, and BMP signaling pathways. More recently, the crucial role played by chromatin remodeling genes in the pathogenesis of CMI has increasingly emerged.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this paper, we discuss a familial case of CMI and a single patient, harboring variants in chromatin remodeling genes, identified by whole exome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The first is a family with three affected members and one sibling with a cerebellar tonsil herniation of &lt;\u20095\u2009mm. The three CMI patients harbor a heterozygous missense variant in the <jats:italic>SETD2<\/jats:italic> gene, whose truncating variants are responsible for Luscan\u2013Lumish syndrome. A second variant in <jats:italic>HP1BP3<\/jats:italic>, a gene not previously associated with human pathology, with evidence of skeletal anomalies in mice models, was found in the three patients and also in the girl with a herniation of &lt;\u20095\u2009mm. The second case is a proband with a de novo variant in <jats:italic>KMT2A<\/jats:italic>, associated with Wiedemann\u2013Steiner syndrome, in which anomalies of the craniocervical junction are described.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>We highlight the importance of chromatin remodeling genes in both isolated and syndromic CMI and suggest the potential role of <jats:italic>HP1BP3<\/jats:italic> as a possible modifier gene in CMI pathogenesis, even if this association needs to be further clarified.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2446","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T11:41:57Z","timestamp":1738755717000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variants in Chromatin Remodeling Genes Are Involved in Patients With Chiari Malformation Type 1"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3933-0597","authenticated-orcid":false,"given":"Ferruccio","family":"Romano","sequence":"first","affiliation":[{"name":"Genomics and Clinical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Cerminara","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-3750","authenticated-orcid":false,"given":"Patrizia","family":"De Marco","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Iacomino","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Di Duca","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Domenico","family":"Tortora","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Neuroradiology Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Pavanello","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianluca","family":"Piatelli","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federico","family":"Zara","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-6514","authenticated-orcid":false,"given":"Aldamaria","family":"Puliti","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"},{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3097-0388","authenticated-orcid":false,"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[{"name":"Genomics and Clinical Genetics Unit IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"issue":"5","key":"e_1_2_9_2_1","first-page":"299","article-title":"Ventriculomegaly in Neurofibromatosis\u20101. 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