{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:54:23Z","timestamp":1773035663144,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["309548"],"award-info":[{"award-number":["309548"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["101080249"],"award-info":[{"award-number":["101080249"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N025431\/1"],"award-info":[{"award-number":["MR\/N025431\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["CFI\u2010JELF 38412"],"award-info":[{"award-number":["CFI\u2010JELF 38412"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Pontocerebellar hypoplasia (PCH) encompasses a heterogeneous group of neurodevelopmental disorders, currently comprising 28 subtypes listed in the Online Mendelian Inheritance in Man (OMIM) database (as of May 2025). No clinical phenotype has been associated with the\n                      <jats:italic>TTC1<\/jats:italic>\n                      gene in OMIM. In this report, we present four female patients from two unrelated families exhibiting PCH with cerebral periventricular leukomalacia and additional clinical features potentially linked to\n                      <jats:italic>TTC1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case Presentations<\/jats:title>\n                    <jats:p>All four affected individuals presented with global developmental delay. Physical examination revealed axial hypotonia, microcephaly and esotropia. Neuroimaging (brain MRI) consistently demonstrated PCH, reduced white matter volume and ventriculomegaly secondary to periventricular leukomalacia. Genomic DNA extracted from peripheral blood samples of the affected individuals, their unaffected parents and siblings was analyzed using trio\u2010based whole\u2010exome sequencing. Variant prioritization was performed via the RD\u2010Connect Genome\u2013Phenome Analysis Platform, which identified a homozygous missense variant in TTC1 (NM_003314.3: c.784\u2009T\u2009&gt;\u2009G, p.Phe262Val) in all affected individuals. The variant was present in the heterozygous state in all parents and unaffected siblings. This variant is classified as likely pathogenic in the ClinVar database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>\n                      Our findings in four patients confirm that this variant in the\n                      <jats:italic>TTC1<\/jats:italic>\n                      gene may be associated with PCH and cerebral periventricular leukomalacia. To our knowledge, this is the first report implicating\n                      <jats:italic>TTC1<\/jats:italic>\n                      in congenital brain malformations. We propose that\n                      <jats:italic>TTC1<\/jats:italic>\n                      should be considered a candidate gene in the genetic evaluation of patients with PCH and related cerebral abnormalities.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jdn.70031","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T14:45:26Z","timestamp":1752072326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pontocerebellar Hypoplasia and Periventricular Leukomalacia Associated With p.Phe262Val Homozygous Variant in TTC1 Gene: A Report of 4 Cases"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5028-9995","authenticated-orcid":false,"given":"Gamze","family":"Sar\u0131kaya\u00a0Uzan","sequence":"first","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"},{"name":"Department of Pediatric Neurology Health Sciences University Tepecik Training and Research Hospital  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9218-0518","authenticated-orcid":false,"given":"Ali\u00a0Han","family":"Yaram\u0131\u015f","sequence":"additional","affiliation":[{"name":"Darge\u00e7it Community Health Center  Mardin Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8526-1477","authenticated-orcid":false,"given":"Ece","family":"S\u00f6nmezler","sequence":"additional","affiliation":[{"name":"International Biomedicine and Genom Institute Dokuz Eyl\u00fcl University  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8020-4884","authenticated-orcid":false,"given":"Semra","family":"H\u0131z\u00a0Kurul","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"},{"name":"International Biomedicine and Genom Institute Dokuz Eyl\u00fcl University  \u0130zmir Turkey"},{"name":"Izmir Biomedicine and Genome Center Dokuz Eylul University Health Campus  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8011-4458","authenticated-orcid":false,"given":"Aysenur","family":"Yaram\u0131\u015f","sequence":"additional","affiliation":[{"name":"Beth Israel Deaconess Medical Center Neurology Department Harvard University  Boston Massachusetts USA"},{"name":"Koc University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8355-1411","authenticated-orcid":false,"given":"Ulu\u00e7","family":"Yi\u015f","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-6297","authenticated-orcid":false,"given":"\u00c7a\u011fatay","family":"G\u00fcnay","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics Dokuz Eyl\u00fcl University Faculty of Medicine  \u0130zmir Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2324-8001","authenticated-orcid":false,"given":"Hanns","family":"Lochmuller","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Medicine, Children's Hospital of Eastern Ontario Research Institute, The Ottawa Hospital University of Ottawa  Ottawa Canada"},{"name":"Centro Nacional de An\u00e1lisis Gen\u00f3mico (CNAG)  Barcelona Spain"},{"name":"Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine University of Freiburg  Freiburg Germany"},{"name":"Division of Neurology, Department of Medicine, The Ottawa Hospital; 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