{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:50:35Z","timestamp":1790275835316,"version":"4.1.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/501100005075","name":"Universitair Medisch Centrum Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005075","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Recipient of a Junior Scientific Masterclass MD\/PhD scholarship of the University Medical Center Groningen Crowdfunding organised by Chromosome 6 parents"},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["113312101"],"award-info":[{"award-number":["113312101"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Hum Genet"],"published-print":{"date-parts":[[2021,11]]},"DOI":"10.1038\/s41431-021-00948-0","type":"journal-article","created":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T02:03:31Z","timestamp":1630289011000},"page":"1669-1676","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["TAB2 deletions and variants cause a highly recognisable syndrome with mitral valve disease, cardiomyopathy, short stature and hypermobility"],"prefix":"10.1038","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7693-1288","authenticated-orcid":false,"given":"Aafke","family":"Engwerda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika K. S. M.","family":"Leenders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Frentz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien A.","family":"Terhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"L\u00f6hner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert B. A.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trijnie","family":"Dijkhuizen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvonne J.","family":"Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4350-8106","authenticated-orcid":false,"given":"Tuula","family":"Rinne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1493-2998","authenticated-orcid":false,"given":"Maarten P.","family":"van den Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc T. R.","family":"Roofthooft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-3966","authenticated-orcid":false,"given":"Patrick","family":"Deelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8744-1305","authenticated-orcid":false,"given":"Conny M. A.","family":"van Ravenswaaij-Arts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2528-2203","authenticated-orcid":false,"given":"Wilhelmina S.","family":"Kerstjens-Frederikse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,30]]},"reference":[{"key":"948_CR1","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.ajhg.2010.04.011","volume":"86","author":"B Thienpont","year":"2010","unstructured":"Thienpont B, Zhang L, Postma AV, Breckpot J, Tranchevent L, Van Loo P, et al. Haploinsufficiency of TAB2 causes congenital heart defects in humans. Am J Hum Genet. 2010;86:839\u201349.","journal-title":"Am J Hum Genet"},{"key":"948_CR2","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1002\/ajmg.a.38254","volume":"173","author":"A Cheng","year":"2017","unstructured":"Cheng A, Dinulos MBP, Neufeld\u2010Kaiser W, Rosenfeld J, Kyriss M, Madan\u2010Khetarpal S, et al. 6q25.1 (TAB2) microdeletion syndrome: congenital heart defects and cardiomyopathy. Am J Med Genet Part A. 2017;173:1848\u201357. Jul.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR3","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/cge.13032","volume":"93","author":"M Ritelli","year":"2018","unstructured":"Ritelli M, Morlino S, Giacopuzzi E, Bernardini L, Torres B, Santoro G, et al. A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations. Clin Genet. 2018;93:126\u201333.","journal-title":"Clin Genet"},{"key":"948_CR4","doi-asserted-by":"publisher","first-page":"11473","DOI":"10.1073\/pnas.1324128111","volume":"111","author":"P Chen","year":"2014","unstructured":"Chen P, Yin J, Yu H, Yuan T, Fernandez M, Yung CK, et al. Next-generation sequencing identifies rare variants associated with Noonan syndrome. Proc Natl Acad Sci USA. 2014;111:11473\u20138. 8-5.","journal-title":"Proc Natl Acad Sci USA"},{"key":"948_CR5","doi-asserted-by":"crossref","unstructured":"Engwerda A, Frentz B, den Ouden AL, Flapper BCT, Swertz MA, Gerkes EH, et al. The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports. Eur J Hum Genet. 2018;26:1478\u201389.","DOI":"10.1038\/s41431-018-0172-9"},{"key":"948_CR6","doi-asserted-by":"publisher","first-page":"S12","DOI":"10.1186\/1471-2105-11-S12-S12","volume":"11","author":"MA Swertz","year":"2010","unstructured":"Swertz MA, Dijkstra M, Adamusiak T, van der Velde JK, Kanterakis A, Roos ET, et al. The MOLGENIS toolkit: rapid prototyping of biosoftware at the push of a button. BMC Bioinform. 2010;11:S12\u2013S12. December 21Suppl 12.","journal-title":"BMC Bioinform"},{"key":"948_CR7","doi-asserted-by":"crossref","unstructured":"Corsten-Janssen N, Bouman K, Diphoorn JCD, Scheper AJ, Kinds R, El Mecky J, et al. A prospective study on rapid exome sequencing as a diagnostic test for multiple congenital anomalies on fetal ultrasound. Prenat Diagn. 2020;40:1300\u20139.","DOI":"10.1002\/pd.5781"},{"key":"948_CR8","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","volume":"367","author":"J de Ligt","year":"2012","unstructured":"de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012;367:1921\u20139. November 15.","journal-title":"N Engl J Med"},{"key":"948_CR9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41431-019-0427-0","volume":"28","author":"PA Terhal","year":"2020","unstructured":"Terhal PA, Vlaar JM, Middelkamp S, Nievelstein RAJ, Nikkels PGJ, Ross J, et al. Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia. Eur J Hum Genet. 2020;28:31\u201339. January 01.","journal-title":"Eur J Hum Genet"},{"key":"948_CR10","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1002\/ajmg.1320530213","volume":"53","author":"I Van Der Burgt","year":"1994","unstructured":"Van Der Burgt I, Berends E, Lommen E, Van Beersum S, Hamel B, Mariman E. Clinical and molecular studies in a large Dutch family with Noonan syndrome. Am J Med Genet. 1994;53:187\u201391. Nov 1.","journal-title":"Am J Med Genet"},{"key":"948_CR11","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1002\/ajmg.a.32144","volume":"146A","author":"MJM Nowaczyk","year":"2008","unstructured":"Nowaczyk MJM, Carter MT, Xu J, Huggins M, Raca G, Das S, et al. Paternal deletion 6q24.3: A new congenital anomaly syndrome associated with intrauterine growth failure, early developmental delay and characteristic facial appearance. Am J Med Genet Part A. 2008;146A:354\u201360. Feb 1.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR12","doi-asserted-by":"publisher","first-page":"2378","DOI":"10.1002\/ajmg.a.36631","volume":"164","author":"VA Meloni","year":"2014","unstructured":"Meloni VA, Guilherme RS, Oliveira MM, Migliavacca M, Takeno SS, Sobreira NLM, et al. Cytogenomic delineation and clinical follow\u2010up of two siblings with an 8.5\u2009Mb 6q24.2\u2010q25.2 deletion inherited from a paternal insertion. Am J Med Genet Part A. 2014;164:2378\u201384. Sep.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-020-01404-5","volume":"20","author":"A Cheng","year":"2020","unstructured":"Cheng A, Neufeld-Kaiser W, Byers PH, Liu YJ. 6q25.1 (TAB2) microdeletion is a risk factor for hypoplastic left heart: a case report that expands the phenotype. BMC Cardiovas Disord. 2020;20:137. Mar 17.","journal-title":"BMC Cardiovas Disord"},{"key":"948_CR14","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/j.ejmg.2007.03.003","volume":"50","author":"R Caselli","year":"2007","unstructured":"Caselli R, Mencarelli MA, Papa FT, Uliana V, Schiavone S, Strambi M, et al. A 2.6 Mb deletion of 6q24.3\u201325.1 in a patient with growth failure, cardiac septal defect, thin upperlip and asymmetric dysmorphic ears. Eur J Med Genet. 2007;50:315\u201321.","journal-title":"Eur J Med Genet"},{"key":"948_CR15","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1002\/ajmg.a.37118","volume":"167","author":"V Salpietro","year":"2015","unstructured":"Salpietro V, Ruggieri M, Mankad K, Di Rosa G, Granata F, Loddo I, et al. A de novo 0.63\u2009Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity. Am J Med Genet Part A. 2015;167:2042\u201351. Sep.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR16","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1002\/ajmg.a.31425","volume":"140A","author":"A Bisgaard","year":"2006","unstructured":"Bisgaard A, Kirchhoff M, T\u00fcmer Z, Jepsen B, Br\u00f8ndum\u2010Nielsen K, Cohen M, et al. Additional chromosomal abnormalities in patients with a previously detected abnormal karyotype, mental retardation, and dysmorphic features. Am J Med Genet Part A. 2006;140A:2180\u20137. Oct 15.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR17","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1002\/ajmg.a.37210","volume":"167","author":"K Weiss","year":"2015","unstructured":"Weiss K, Applegate C, Wang T, Batista DAS. Familial TAB2 microdeletion and congenital heart defects including unusual valve dysplasia and tetralogy of fallot. Am J Med Genet Part A. 2015;167:2702\u20136. Nov.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12881-015-0212-z","volume":"16","author":"S Stagi","year":"2015","unstructured":"Stagi S, Lapi E, Pantaleo M, Carella M, Petracca A, De Crescenzo A, et al. A new case of de novo 6q24.2-q25.2 deletion on paternal chromosome 6 with growth hormone deficiency: a twelve-year follow-up and literature review. BMC Med Genet. 2015;16:69\u2013z.","journal-title":"BMC Med Genet"},{"key":"948_CR19","doi-asserted-by":"crossref","unstructured":"Permanyer E, Laurie S, Blasco-Lucas A, Maldonado G, Amador-Catalan A, Ferrer-Curriu G, et al. A single nucleotide deletion resulting in a frameshift in exon 4 of TAB2 is associated with a polyvalular syndrome. Eur J Med Genet. 2020;63:103854.","DOI":"10.1016\/j.ejmg.2020.103854"},{"key":"948_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-019-01322-1","volume":"20","author":"J Chen","year":"2020","unstructured":"Chen J, Yuan H, Xie K, Wang X, Tan L, Zou Y, et al. A novel TAB2 nonsense mutation (p.S149X) causing autosomal dominant congenital heart defects: a case report of a Chinese family. BMC Cardiovasc Disord. 2020;20:27. Jan 20.","journal-title":"BMC Cardiovasc Disord"},{"key":"948_CR21","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/mgg3.401","volume":"6","author":"TR Caulfield","year":"2018","unstructured":"Caulfield TR, Richter JE, Brown EE, Mohammad AN, Judge DP, Atwal PS. Protein molecular modeling techniques investigating novel TAB2 variant R347X causing cardiomyopathy and congenital heart defects in multigenerational family. Mol Genet Genom Med. 2018;6:666\u201372. Jul.","journal-title":"Mol Genet Genom Med"},{"key":"948_CR22","doi-asserted-by":"publisher","first-page":"2324","DOI":"10.1016\/j.jacc.2018.08.2171","volume":"72","author":"C Vasilescu","year":"2018","unstructured":"Vasilescu C, Ojala TH, Brilhante V, Ojanen S, Hinterding HM, Palin E, et al. Genetic basis of severe childhood-onset cardiomyopathies. J Am Coll Cardiol. 2018;72:2324\u201338. Nov 6.","journal-title":"J Am Coll Cardiol"},{"key":"948_CR23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1111\/chd.12400","volume":"11","author":"JP Ackerman","year":"2016","unstructured":"Ackerman JP, Smestad JA, Tester DJ, Qureshi MY, Crabb BA, Mendelsohn NJ, et al. Whole exome sequencing, familial genomic triangulation, and systems biology converge to identify a novel nonsense mutation in TAB2\u2010encoded TGF\u2010beta activated kinase 1 in a child with Polyvalvular Syndrome. Congenit Heart Dis. 2016;11:452\u201361. Sep.","journal-title":"Congenit Heart Dis"},{"key":"948_CR24","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.ajhg.2016.05.024","volume":"99","author":"E Wade","year":"2016","unstructured":"Wade E, Daniel P, Jenkins Z, McInerney-Leo A, Leo P, Morgan T, et al. Mutations in MAP3K7 that Alter the activity of the TAK1 signaling complex cause frontometaphyseal dysplasia. Am J Hum Genet. 2016;99:392\u2013406. Aug 4.","journal-title":"Am J Hum Genet"},{"key":"948_CR25","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1002\/ajmg.a.38267","volume":"173","author":"EM Wade","year":"2017","unstructured":"Wade EM, Jenkins ZA, Daniel PB, Morgan T, Addor MC, Ad\u00e9s LC, et al. Autosomal dominant frontometaphyseal dysplasia: Delineation of the clinical phenotype. Am J Med Genet Part A. 2017;173:1739\u201346.","journal-title":"Am J Med Genet Part A"},{"key":"948_CR26","unstructured":"McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD). Online Mendelian Inheritance in Man, OMIM\u00ae. https:\/\/omim.org\/. Accessed 1 July 2020."},{"key":"948_CR27","doi-asserted-by":"publisher","first-page":"2837","DOI":"10.1038\/s41467-019-10649-4","volume":"10","author":"P Deelen","year":"2019","unstructured":"Deelen P, van Dam S, Herkert JC, Karjalainen JM, Brugge H, Abbott KM, et al. Improving the diagnostic yield of exome- sequencing by predicting gene-phenotype associations using large-scale gene expression analysis. Nat Commun. 2019;10:2837\u20134.","journal-title":"Nat Commun"},{"key":"948_CR28","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1002\/humu.21492","volume":"32","author":"F Lepri","year":"2011","unstructured":"Lepri F, De Luca A, Stella L, Rossi C, Baldassarre G, Pantaleoni F, et al. SOS1 mutations in Noonan syndrome: molecular spectrum, structural insights on pathogenic effects, and genotype\u2013phenotype correlations. Hum Mutat. 2011;32:760\u201372.","journal-title":"Hum Mutat"},{"key":"948_CR29","doi-asserted-by":"publisher","first-page":"2246","DOI":"10.1182\/blood-2002-07-2260","volume":"101","author":"C Orelio","year":"2003","unstructured":"Orelio C, Dzierzak E. Identification of 2 novel genes developmentally regulated in the mouse aorta-gonad-mesonephros region. Blood. 2003;101:2246\u20139. Jan 1.","journal-title":"Blood"},{"key":"948_CR30","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/s41431-017-0079-x","volume":"26","author":"S Morlino","year":"2018","unstructured":"Morlino S, Castori M, Dordoni C, Cinquina V, Santoro G, Grammatico P, et al. A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder. Eur J Hum Genet: EJHG. 2018;26:582\u20136. Apr.","journal-title":"Eur J Hum Genet: EJHG"},{"key":"948_CR31","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1042\/BCJ20170288","volume":"474","author":"J Zhang","year":"2017","unstructured":"Zhang J, Macartney T, Peggie M, Cohen P. Interleukin-1 and TRAF6-dependent activation of TAK1 in the absence of TAB2 and TAB3. Biochem J. 2017;474:2235\u201348. June 26.","journal-title":"Biochem J"}],"container-title":["European Journal of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41431-021-00948-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-021-00948-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41431-021-00948-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:05:01Z","timestamp":1635811501000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41431-021-00948-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,30]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["948"],"URL":"https:\/\/doi.org\/10.1038\/s41431-021-00948-0","relation":{},"ISSN":["1018-4813","1476-5438"],"issn-type":[{"value":"1018-4813","type":"print"},{"value":"1476-5438","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,30]]},"assertion":[{"value":"14 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 August 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2021","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"}},{"value":"The accredited Medical Ethics Review Committee of the University Medical Center Groningen waived full ethical evaluation because, according to Dutch guidelines, no ethical approval is necessary if medical information that was already available is used anonymously and no extra tests have to be performed.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}