{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T12:37:49Z","timestamp":1789043869382,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Cardiospondylocarpofacial syndrome (CSCFS) is an extremely rare autosomal dominant disorder resulting from variant in the <jats:italic>MAP3K7<\/jats:italic> gene, which encodes the transforming growth factor-\u03b2-activated kinase 1 (TAK1). Only 26 cases of CSCFS have been reported worldwide. The main manifestations are growth retardation, hypotonia, dysmorphic facial features, skeletal and limb abnormalities, cardiac septal defects with valve dysplasia, cardiomyopathy, and deafness with inner ear malformations. In this study, we recruited an unrelated Chinese family with a patient diagnosed with CSCFS. Whole exome sequencing revealed a novel heterozygous variant, c.142G\u2009&amp;gt;\u2009A[p. (Gly48Arg)], in the <jats:italic>MAP3K7<\/jats:italic> gene. The variant was confirmed by Sanger sequencing to be absent in other family members and is <jats:italic>de novo<\/jats:italic>. The patient described here has a similar dysmorphology profile to that associated with CSCFS. Compared with reported cases of CSCFS, our patient presented with new complications of short tongue tie, brain abnormalities including asymmetrical cerebral hemispheres with widening of the right frontotemporal exoptic hiatus, intestinal obstruction and intussusception. In addition, scoliosis, vertebral abnormalities, carpal\/tarsal fusion, pectus excavatum, and cervical spine fusion were not found in our patient. The molecular diagnosis in this patient extends the known genetic spectrum of CSCFS. Furthermore, the specific manifestations in this case offer valuable additional clinical details regarding the syndrome.<\/jats:p>","DOI":"10.3389\/fped.2025.1651803","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:36:01Z","timestamp":1755668161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic diagnosis and clinical characteristics analysis of cardiospondylocarpofacial syndrome in a Chinese family"],"prefix":"10.3389","volume":"13","author":[{"given":"Qi","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wurui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunzhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinle","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.biocel.2009.12.023","article-title":"The TAK1-TRAF6 signalling pathway","volume":"42","author":"Landstr\u00f6m","year":"2010","journal-title":"Int J Biochem Cell Biol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3918","DOI":"10.1074\/jbc.M608867200","article-title":"TAK1-dependent signaling requires functional interaction with TAB2\/TAB3","volume":"282","author":"Besse","year":"2007","journal-title":"J Biol Chem"},{"key":"B3","doi-asserted-by":"publisher","first-page":"a011254","DOI":"10.1101\/cshperspect.a011254","article-title":"MAP kinase pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/s1097-2765(00)80244-0","article-title":"TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway","volume":"5","author":"Takaesu","year":"2000","journal-title":"Mol Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1074\/jbc.M109.090522","article-title":"Transforming growth factor beta-activated kinase 1 (TAK1) kinase adaptor, TAK1-binding protein 2, plays dual roles in TAK1 signaling by recruiting both an activator and an inhibitor of TAK1 kinase in tumor necrosis factor signaling pathway","volume":"285","author":"Broglie","year":"2010","journal-title":"J Biol Chem"},{"key":"B6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s10495-018-1490-7","article-title":"TAK1 mediates convergence of cellular signals for death and survival","volume":"24","author":"Aashaq","year":"2019","journal-title":"Apoptosis"},{"key":"B7","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.ajhg.2016.05.024","article-title":"Mutations in MAP3K7 that alter the activity of the TAK1 signaling complex cause frontometaphyseal dysplasia","volume":"99","author":"Wade","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1016\/j.ajhg.2016.06.005","article-title":"Heterozygous mutations in MAP3K7, encoding TGF-\u03b2-activated kinase 1, cause cardiospondylocarpofacial syndrome","volume":"99","author":"Le Goff","year":"2016","journal-title":"Am J Hum Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/ng1119","article-title":"Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans","volume":"33","author":"Robertson","year":"2003","journal-title":"Nat Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41431-017-0079-x","article-title":"A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder","volume":"26","author":"Morlino","year":"2018","journal-title":"Eur J Hum Genet"},{"key":"B11","doi-asserted-by":"publisher","first-page":"165742","DOI":"10.1016\/j.bbadis.2020.165742","article-title":"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","volume":"1866","author":"Micale","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"a005207","DOI":"10.1101\/mcs.a005207","article-title":"A novel variant in MAP3K7 associated with an expanded cardiospondylocarpofacial syndrome phenotype","volume":"6","author":"AbuBakr","year":"2020","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"B13","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/ajmg.a.62516","article-title":"Expanding the phenotypic spectrum of cardiospondylocarpofacial syndrome: from a detailed clinical and radiological observation of a boy with a novel missense variant in MAP3K7","volume":"188","author":"Minatogawa","year":"2022","journal-title":"Am J Med Genet A"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1002\/humu.24425","article-title":"The MAP3K7 gene: further delineation of clinical characteristics and genotype\/phenotype correlations","volume":"43","author":"van Woerden","year":"2022","journal-title":"Hum Mutat"},{"key":"B15","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1002\/pd.6358","article-title":"Early and severe tricuspid valve dysplasia in a fetus with cardiospondylocarpofacial syndrome due to a variant c.616T\u2009>\u2009G p.(Tyr206Asp) in MAP3K7","volume":"43","author":"Vasishta","year":"2023","journal-title":"Prenat Diagn"},{"key":"B16","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1111\/cge.14253","article-title":"A novel MAP3K7 mutation in a child with cardiospondylocarpofacial syndrome and orofacial clefting","volume":"103","author":"Shepherd","year":"2023","journal-title":"Clin Genet"},{"key":"B17","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1038\/s41439-024-00265-0","article-title":"A severe case of cardiospondylocarpofacial syndrome with a novel MAP3K7 variant","volume":"11","author":"Nyuzuki","year":"2024","journal-title":"Hum Genome Var"},{"key":"B18","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/s0022-3476(66)80418-3","article-title":"Congenital heart disease, deafness, and skeletal malformations: a new syndrome?","volume":"68","author":"Forney","year":"1966","journal-title":"J Pediatr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1002\/ajmg.a.33277","article-title":"Postnatal growth retardation, facial dysmorphism, spondylocarpal synostosis, cardiac defect, and inner ear malformation (cardiospondylocarpofacial syndrome?)--a distinct syndrome?","author":"Sousa","year":"2010","journal-title":"Am J Med Genet A"},{"key":"B21","doi-asserted-by":"publisher","first-page":"13467","DOI":"10.1074\/jbc.M112.431775","article-title":"TGF-\u03b2-activated kinase 1 (Tak1) mediates agonist-induced Smad activation and linker region phosphorylation in embryonic craniofacial neural crest-derived cells","volume":"288","author":"Yumoto","year":"2013","journal-title":"J Biol Chem"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.4049\/jimmunol.181.2.1143","article-title":"Enterocyte-derived TAK1 signaling prevents epithelium apoptosis and the development of ileitis and colitis","volume":"181","author":"Kajino-Sakamoto","year":"2008","journal-title":"J Immunol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1007\/s10571-014-0148-4","article-title":"Wogonin inhibits LPS-induced inflammatory responses in rat dorsal root ganglion neurons via inhibiting TLR4-MyD88-TAK1-mediated NF-\u03baB and MAPK signaling pathway","volume":"35","author":"Chen","year":"2015","journal-title":"Cell Mol Neurobiol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1651803\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:36:01Z","timestamp":1755668161000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1651803\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":23,"alternative-id":["10.3389\/fped.2025.1651803"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1651803","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]},"article-number":"1651803"}}