{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T01:52:57Z","timestamp":1784425977347,"version":"3.55.0"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,28]],"date-time":"2024-04-28T00:00:00Z","timestamp":1714262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    RASopathies represent a distinct class of neurodevelopmental syndromes caused by germline variants in the Ras\/MAPK pathways. Recently, a novel disease\u2010gene association was implicated in MAPK kinase kinase kinase 4 (\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    ), which regulates the upstream signals of the MAPK pathways. However, to our knowledge, only two studies have reported the genotype\u2013phenotype relationships in the\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    \u2010related disorder. This study reports on a Korean boy harboring a novel de novo missense variant in\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    (NM_001242559:c.569G&gt;T, p.Gly190Val), revealed by trio exome sequencing, and located in the hotspot of the protein kinase domain. The patient exhibited various clinical features, including craniofacial dysmorphism, language delay, congenital heart defects, genitourinary anomalies, and sagittal craniosynostosis. Our study expands the phenotypic association of the\n                    <jats:italic>MAP4K4<\/jats:italic>\n                    \u2010related disorder to include syndromic craniosynostosis, thereby providing further insights into the role of the RAS\/MAPK pathways in the development of premature fusion of calvarial sutures.\n                  <\/jats:p>","DOI":"10.1111\/cge.14539","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:44:35Z","timestamp":1714351475000},"page":"199-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Syndromic craniosynostosis caused by a novel missense variant in\n                    <i>MAP4K4<\/i>\n                    : Expanding the genotype\u2013phenotype relationship in\n                    <scp>RASopathies<\/scp>"],"prefix":"10.1111","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-7803","authenticated-orcid":false,"given":"Jihoon G.","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Yonsei University College of Medicine and Gangnam Severance Hospital  Seoul Republic of Korea"},{"name":"Department of Pharmacology Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Woo","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine  Seoul Republic of Korea"},{"name":"Department of Pediatric Neurosurgery, Craniofacial Reforming and Reconstruction Clinic Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Won","family":"Shim","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurosurgery, Craniofacial Reforming and Reconstruction Clinic Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3756-4809","authenticated-orcid":false,"given":"Yong Oock","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Plastic and Reconstructive Surgery Institute for Human Tissue Restoration, Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7436-012X","authenticated-orcid":false,"given":"Min Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2009.04.001"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-091212-153523"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14323"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.33"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade0631"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-022-02497-y"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.128.9.1559"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyz470"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.138115.112"},{"key":"e_1_2_10_12_1","first-page":"1633","article-title":"Homozygous 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