{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:31:05Z","timestamp":1792816265988,"version":"4.5.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genome Var"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Cardiospondylocarpofacial syndrome (CSCFS) is a congenital malformation characterized by growth retardation, facial features, short toes with carpal and tarsal fusion, extensive posterior neck vertebral fusion, congenital heart disease, and deafness. Here, we report a severe case of CSCFS with a novel variant, p.Thr187Ile, in <jats:italic>MAP3K7<\/jats:italic>. Thr187 is the main phosphorylation site for TGF-beta-activated kinase 1 encoded by <jats:italic>MAP3K7<\/jats:italic>, and this variant may cause significant abnormalities in downstream signaling.<\/jats:p>","DOI":"10.1038\/s41439-024-00265-0","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T04:36:26Z","timestamp":1708576586000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A severe case of cardiospondylocarpofacial syndrome with a novel MAP3K7 variant"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1502-0875","authenticated-orcid":false,"given":"Hiromi","family":"Nyuzuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Ozawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5882-661X","authenticated-orcid":false,"given":"Keisuke","family":"Nagasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoo","family":"Ogi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6468-901X","authenticated-orcid":false,"given":"Jun","family":"Tohyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8828-8085","authenticated-orcid":false,"given":"Takeshi","family":"Ikeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,22]]},"reference":[{"key":"265_CR1","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.ajhg.2016.06.005","volume":"99","author":"C Le Goff","year":"2016","unstructured":"Le Goff, C. et al. Heterozygous mutations in MAP3K7, encoding TGF-\u03b2-Activated Kinase 1, cause cardiospondylocarpofacial syndrome. Am. J. Hum. Genet. 99, 407\u2013413 (2016).","journal-title":"Am. J. Hum. Genet"},{"key":"265_CR2","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41431-017-0079-x","volume":"26","author":"S Morlino","year":"2018","unstructured":"Morlino, S. et al. A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder. Eur. J. Hum. Genet. 26, 582\u2013586 (2018).","journal-title":"Eur. J. Hum. Genet."},{"key":"265_CR3","doi-asserted-by":"publisher","first-page":"a005207","DOI":"10.1101\/mcs.a005207","volume":"6","author":"F AbuBakr","year":"2020","unstructured":"AbuBakr, F., Jeffries, L., Ji, W., McGrath, J. M. & Lakhani, S. A. A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype. Cold Spring Harb. Mol. Case Stud. 6, a005207 (2020).","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"265_CR4","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/ajmg.a.62516","volume":"188","author":"M Minatogawa","year":"2022","unstructured":"Minatogawa, M. et al. Expanding the phenotypic spectrum of cardiospondylocarpofacial syndrome: from a detailed clinical and radiological observation of a boy with a novel missense variant in MAP3K7. Am. J. Med. Genet. A 188, 350\u2013356 (2022).","journal-title":"Am. J. Med. Genet. A"},{"key":"265_CR5","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013424 (2015).","journal-title":"Genet. Med."},{"key":"265_CR6","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.ajhg.2016.05.024","volume":"99","author":"EM Wade","year":"2016","unstructured":"Wade, E. M. et al. Mutations in MAP3K7 that alter the activity of the TAK1 signaling complex cause frontometaphyseal dysplasia. Am. J. Hum. Genet. 99, 392\u2013406 (2016).","journal-title":"Am. J. Hum. Genet."},{"key":"265_CR7","doi-asserted-by":"publisher","first-page":"25753","DOI":"10.1074\/jbc.M109.093468","volume":"285","author":"R Scholz","year":"2010","unstructured":"Scholz, R. et al. Autoactivation of transforming growth factor beta-activated kinase 1 is a sequential bimolecular process. J. Biol. Chem. 285, 25753\u201325766 (2010).","journal-title":"J. Biol. Chem."},{"key":"265_CR8","doi-asserted-by":"publisher","first-page":"7359","DOI":"10.1074\/jbc.275.10.7359","volume":"275","author":"K Kishimoto","year":"2000","unstructured":"Kishimoto, K., Matsumoto, K. & Ninomiya-Tsuji, J. TAK1 mitogen-activated protein kinase kinase kinase is activated by autophosphorylation within its activation loop. J. Biol. Chem. 275, 7359\u20137364 (2000).","journal-title":"J. Biol. Chem."},{"key":"265_CR9","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1002\/iub.1078","volume":"64","author":"L Dai","year":"2012","unstructured":"Dai, L., Aye Thu, C., Liu, X. Y., Xi, J. & Cheung, P. C. TAK1, more than just innate immunity. IUBMB Life 64, 825\u2013834 (2012).","journal-title":"IUBMB Life"},{"key":"265_CR10","doi-asserted-by":"publisher","first-page":"165742","DOI":"10.1016\/j.bbadis.2020.165742","volume":"1866","author":"L Micale","year":"2020","unstructured":"Micale, L. et al. Insights into the molecular pathogenesis of cardiospondylocarpofacial syndrome: MAP3K7 c.737-7A > G variant alters the TGF\u03b2-mediated \u03b1-SMA cytoskeleton assembly and autophagy. Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165742 (2020).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."}],"container-title":["Human Genome Variation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41439-024-00265-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41439-024-00265-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41439-024-00265-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T08:20:44Z","timestamp":1736929244000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41439-024-00265-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,22]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["265"],"URL":"https:\/\/doi.org\/10.1038\/s41439-024-00265-0","relation":{},"ISSN":["2054-345X"],"issn-type":[{"value":"2054-345X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,22]]},"assertion":[{"value":"12 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 February 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}