{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:38:33Z","timestamp":1792640313409,"version":"4.5.0"},"reference-count":14,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Meier\u2010Gorlin syndrome (MGORS) is a rare primordial dwarfism syndrome characterized by the triad of pre\u2010 and postnatal growth restriction, microtia, and patellar aplasia or hypoplasia. Pathogenic variants in genes involved in DNA replication licensing and initiation have been implicated in MGORS, including the uncommon disease\u2010associated gene\n                    <jats:italic>CDC6<\/jats:italic>\n                    , for which only two affected families have been reported to date. We report a male infant born at 37\u2009weeks' gestation to a 40\u2010year\u2010old primigravida via cesarean delivery due to intrauterine growth restriction and fetal intolerance of labor. He presented with severe proportionate short stature (40\u2009cm at birth;\n                    <jats:italic>Z<\/jats:italic>\n                    score \u22125.22), microcephaly, bilateral microtia, cryptorchidism, hypospadias, nonpalpable patellae, and characteristic facial features including a tiny mouth and short palpebral fissures. Cardiac evaluation was normal. He developed persistent respiratory insufficiency requiring prolonged respiratory support and remains hospitalized due to tracheobronchomalacia and chronic respiratory failure. A clinical diagnosis of MGORS was suspected. Targeted gene panel testing identified a heterozygous variant in\n                    <jats:italic>CDC6<\/jats:italic>\n                    , c.920_927del (p.Ser307ThrfsTer9). Trio genome sequencing subsequently identified a second rare intronic variant,\n                    <jats:italic>CDC6<\/jats:italic>\n                    c.461\u201024A&gt;G, and confirmed that the variants were\n                    <jats:italic>in trans<\/jats:italic>\n                    . A minigene splicing assay demonstrated retention of intron 3 associated with c.461\u201024A&gt;G, resulting in a predicted frameshift, p.Thr155LeufsTer8, and likely nonsense\u2010mediated decay. We report the third family with CDC6\u2010associated MGORS and provide functional evidence supporting the pathogenicity of a novel intronic\n                    <jats:italic>CDC6<\/jats:italic>\n                    variant. These findings expand the mutational spectrum of\n                    <jats:italic>CDC6<\/jats:italic>\n                    \u2010related MGORS and highlight the importance of functional studies in the interpretation of noncanonical splice variants.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70334","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T02:54:17Z","timestamp":1792637657000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Meier\u2010GORLIN Syndrome Caused by Compound Heterozygous\n                    <scp>\n                      <i>CDC6<\/i>\n                    <\/scp>\n                    Variants"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2619-0036","authenticated-orcid":false,"given":"Raquel","family":"Neves","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California San Diego  San Diego California USA"},{"name":"Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7673-5111","authenticated-orcid":false,"given":"Meghan R.","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4045-8385","authenticated-orcid":false,"given":"Amie","family":"Siemonek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3598-460X","authenticated-orcid":false,"given":"Adriana","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Diego  San Diego California USA"},{"name":"Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6899-9322","authenticated-orcid":false,"given":"Louise S.","family":"Bicknell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4833-3747","authenticated-orcid":false,"given":"Lynne M.","family":"Bird","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California San Diego  San Diego California USA"},{"name":"Rady Children's Hospital  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.775"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.269"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010015\u20100322\u2010x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2008.09.021"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.169037"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62016"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.08.013"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010023\u201001359\u2010z"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.832500"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx305"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2006231117"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/tacg.S342804"}],"container-title":["American 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