{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:46:25Z","timestamp":1790667985868,"version":"4.1.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2018,5,1]],"date-time":"2018-05-01T00:00:00Z","timestamp":1525132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T00:00:00Z","timestamp":1525737600000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004189","name":"Max-Planck-Gesellschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["UM1HG007301"],"award-info":[{"award-number":["UM1HG007301"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["Gravitation Grant 24.001.006"],"award-info":[{"award-number":["Gravitation Grant 24.001.006"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health Innovation Challenge Fund","award":["HICF-1009-003"],"award-info":[{"award-number":["HICF-1009-003"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT098051"],"award-info":[{"award-number":["WT098051"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hum Genet"],"published-print":{"date-parts":[[2018,5]]},"DOI":"10.1007\/s00439-018-1887-y","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T11:56:15Z","timestamp":1525780575000},"page":"375-388","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder"],"prefix":"10.1007","volume":"137","author":[{"name":"The DDD study","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-3625","authenticated-orcid":false,"given":"Lot","family":"Snijders Blok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Hiatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin M.","family":"Bowling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W.","family":"Prokop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krysta L.","family":"Engel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Nicholas","family":"Cochran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Martina","family":"Bebin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia K.","family":"Bijlsma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A. L.","family":"Ruivenkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien","family":"Terhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen E. H.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemarie","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane A.","family":"Hurst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"McLaughlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Person","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Crunk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F.","family":"Wangler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haley","family":"Streff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Symonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameer M.","family":"Zuberi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine S.","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria R.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Masunga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Hopkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly A.","family":"Dubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xilma R.","family":"Ortiz-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolph","family":"Pfundt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han G.","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon E.","family":"Fisher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tjitske","family":"Kleefstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory M.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,5,8]]},"reference":[{"key":"1887_CR1","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1038\/ejhg.2015.26","volume":"23","author":"A Adegbola","year":"2015","unstructured":"Adegbola A et al (2015) Redefining the MED13L syndrome Eur. J Hum Genet 23:1308\u20131317. \n                    https:\/\/doi.org\/10.1038\/ejhg.2015.26","journal-title":"J Hum Genet"},{"key":"1887_CR2","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/nrm3951","volume":"16","author":"BL Allen","year":"2015","unstructured":"Allen BL, Taatjes DJ (2015) The Mediator complex: a central integrator of transcription. Nat Rev Mol Cell Biol 16:155\u2013166. \n                    https:\/\/doi.org\/10.1038\/nrm3951","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1887_CR3","unstructured":"Andrews CV, Hunter DG, Engle EC (1993) Duane Syndrome. In: Pagon RA et al (eds) GeneReviews(R). Seattle (WA)"},{"key":"1887_CR4","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1038\/ejhg.2013.17","volume":"21","author":"R Asadollahi","year":"2013","unstructured":"Asadollahi R et al (2013) Dosage changes of MED13L further delineate its role in congenital heart defects and intellectual disability. Eur J Hum Genet 21:1100\u20131104. \n                    https:\/\/doi.org\/10.1038\/ejhg.2013.17","journal-title":"Eur J Hum Genet"},{"key":"1887_CR5","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1002\/humu.22837","volume":"36","author":"PYB Au","year":"2015","unstructured":"Au PYB et al (2015) GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in. HNRNPK Hum Mut 36:1009\u20131014. \n                    https:\/\/doi.org\/10.1002\/humu.22837","journal-title":"HNRNPK Hum Mut"},{"key":"1887_CR6","doi-asserted-by":"publisher","unstructured":"Boat TF, Wu JT (eds) (2015) mental disorders and disabilities among low-income children. Washington (DC). \n                    https:\/\/doi.org\/10.17226\/21780","DOI":"10.17226\/21780"},{"key":"1887_CR7","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/ajmg.a.34222","volume":"158A","author":"N Boutry-Kryza","year":"2012","unstructured":"Boutry-Kryza N et al (2012) An 800 kb deletion at 17q23.2 including the MED13 (THRAP1) gene, revealed by aCGH in a patient with a SMC 17. Am J Med Genet A 158A:400\u2013405. \n                    https:\/\/doi.org\/10.1002\/ajmg.a.34222\n                    \n                   p","journal-title":"Am J Med Genet A"},{"key":"1887_CR8","doi-asserted-by":"publisher","unstructured":"Bowling KM et al (2017) Genomic diagnosis for children with intellectual disability and\/or developmental delay. Genome Med 9:43. \n                    https:\/\/doi.org\/10.1186\/s13073-017-0433-1","DOI":"10.1186\/s13073-017-0433-1"},{"key":"1887_CR9","doi-asserted-by":"publisher","unstructured":"Boyle CA et al (2011) Trends in the prevalence of developmental disabilities in US children 1997\u20132008. Pediatrics 127:1034\u20131042. \n                    https:\/\/doi.org\/10.1542\/peds.2010-2989","DOI":"10.1542\/peds.2010-2989"},{"key":"1887_CR10","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/pr.2016.162","volume":"80","author":"A Caro-Llopis","year":"2016","unstructured":"Caro-Llopis A, Rosello M, Orellana C, Oltra S, Monfort S, Mayo S, Martinez F (2016) De novo mutations in genes of mediator complex causing syndromic intellectual disability: mediatorpathy or transcriptomopathy? Pediatr Res 80:809\u2013815. \n                    https:\/\/doi.org\/10.1038\/pr.2016.162","journal-title":"Pediatr Res"},{"key":"1887_CR11","doi-asserted-by":"publisher","unstructured":"Carrera I, Janody F, Leeds N, Duveau F, Treisman JE (2008) Pygopus activates Wingless target gene transcription through the mediator complex subunits Med12 and Med13. Proc Natl Acad Sci USA 105:6644\u20136649. \n                    https:\/\/doi.org\/10.1073\/pnas.0709749105","DOI":"10.1073\/pnas.0709749105"},{"key":"1887_CR12","doi-asserted-by":"publisher","unstructured":"Chen XF et al (2012) Mediator and SAGA have distinct roles in Pol II preinitiation complex assembly and function. Cell Rep 2:1061\u20131067. \n                    https:\/\/doi.org\/10.1016\/j.celrep.2012.10.019","DOI":"10.1016\/j.celrep.2012.10.019"},{"key":"1887_CR13","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1097\/GIM.0b013e3181bd3d90","volume":"11","author":"RD Clark","year":"2009","unstructured":"Clark RD et al (2009) FG syndrome, an X-linked multiple congenital anomaly syndrome: the clinical phenotype and an algorithm for diagnostic testing. Genet Med 11:769\u2013775. \n                    https:\/\/doi.org\/10.1097\/GIM.0b013e3181bd3d90","journal-title":"Genet Med"},{"key":"1887_CR14","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.tibs.2005.03.002","volume":"30","author":"RC Conaway","year":"2005","unstructured":"Conaway RC, Sato S, Tomomori-Sato C, Yao T, Conaway JW (2005) The mammalian Mediator complex and its role in transcriptional regulation. Trends Biochem Sci 30:250\u2013255. \n                    https:\/\/doi.org\/10.1016\/j.tibs.2005.03.002","journal-title":"Trends Biochem Sci"},{"key":"1887_CR15","unstructured":"Daniels DLF, Schwinn M, Benink MK, Galbraith H, Amunugama MD, Jones R, Allen R, Okazaki D, Yamakawa N, Futaba H, Nagase M, Espinosa T, Urh JM, M. (2013) Mutual Exclusivity of MED12\/MED12L, MED13\/13L, and CDK8\/19 paralogs revealed within the CDK-mediator kinase module. J Proteom Bioinf S2"},{"key":"1887_CR16","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1101\/gad.207720.112","volume":"27","author":"MA Davis","year":"2013","unstructured":"Davis MA, Larimore EA, Fissel BM, Swanger J, Taatjes DJ, Clurman BE (2013) The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with. Mediator Genes Dev 27:151\u2013156. \n                    https:\/\/doi.org\/10.1101\/gad.207720.112","journal-title":"Mediator Genes Dev"},{"key":"1887_CR17","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1056\/NEJMoa1206524","volume":"367","author":"J de Ligt","year":"2012","unstructured":"de Ligt J et al (2012) Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 367:1921\u20131929. \n                    https:\/\/doi.org\/10.1056\/NEJMoa1206524","journal-title":"N Engl J Med"},{"key":"1887_CR18","doi-asserted-by":"publisher","unstructured":"Deciphering Developmental Disorders S (2015) Large-scale discovery of novel genetic causes of developmental disorders. Nature 519:223\u2013228. \n                    https:\/\/doi.org\/10.1038\/nature14135","DOI":"10.1038\/nature14135"},{"key":"1887_CR19","doi-asserted-by":"publisher","unstructured":"Deciphering Developmental Disorders S (2017) Prevalence and architecture of de novo mutations in developmental disorders. Nature 542:433\u2013438. \n                    https:\/\/doi.org\/10.1038\/nature21062","DOI":"10.1038\/nature21062"},{"key":"1887_CR20","doi-asserted-by":"publisher","first-page":"D294-300","DOI":"10.1093\/nar\/gkv1291","volume":"44","author":"H Dinkel","year":"2016","unstructured":"Dinkel H et al (2016) ELM 2016\u2014data update and new functionality of the eukaryotic linear motif resource. Nucleic Acids Res 44:D294-300. \n                    https:\/\/doi.org\/10.1093\/nar\/gkv1291","journal-title":"Nucleic Acids Res"},{"key":"1887_CR21","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1093\/hmg\/ddx099","volume":"26","author":"LM Donnio","year":"2017","unstructured":"Donnio LM et al (2017) MED12-related XLID disorders are dose-dependent of immediate early genes (IEGs) expression. Hum Mol Genet 26:2062\u20132075. \n                    https:\/\/doi.org\/10.1093\/hmg\/ddx099","journal-title":"Hum Mol Genet"},{"key":"1887_CR22","doi-asserted-by":"publisher","first-page":"W389-394","DOI":"10.1093\/nar\/gkv332","volume":"43","author":"A Drozdetskiy","year":"2015","unstructured":"Drozdetskiy A, Cole C, Procter J, Barton GJ (2015) JPred4: a protein secondary structure prediction server. Nucleic Acids Res 43:W389-394. \n                    https:\/\/doi.org\/10.1093\/nar\/gkv332","journal-title":"Nucleic Acids Res"},{"key":"1887_CR23","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.sbi.2017.03.013","volume":"47","author":"M Hantsche","year":"2017","unstructured":"Hantsche M, Cramer P (2017) Conserved RNA polymerase II initiation complex structure Curr. Opin Struct Biol 47:17\u201322. \n                    https:\/\/doi.org\/10.1016\/j.sbi.2017.03.013","journal-title":"Opin Struct Biol"},{"key":"1887_CR24","doi-asserted-by":"publisher","unstructured":"Harms FL et al (2017) Mutations in EBF3 disturb transcriptional profiles and cause intellectual disability, ataxia, and facial dysmorphism Am J Hum Genet 100:117\u2013127. \n                    https:\/\/doi.org\/10.1016\/j.ajhg.2016.11.012","DOI":"10.1016\/j.ajhg.2016.11.012"},{"key":"1887_CR25","first-page":"1895","volume":"88","author":"A Ikai","year":"1980","unstructured":"Ikai A (1980) Thermostability and aliphatic index of globular proteins. J Biochem 88:1895\u20131898","journal-title":"J Biochem"},{"key":"1887_CR26","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/nature13908","volume":"515","author":"I Iossifov","year":"2014","unstructured":"Iossifov I et al (2014) The contribution of de novo coding mutations to autism spectrum disorder. Nature 515:216\u2013221. \n                    https:\/\/doi.org\/10.1038\/nature13908","journal-title":"Nature"},{"key":"1887_CR27","doi-asserted-by":"publisher","unstructured":"Kernohan KD et al. (2017) Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene. Hum Mut 38:511\u2013516 \n                    https:\/\/doi.org\/10.1002\/humu.23196","DOI":"10.1002\/humu.23196"},{"key":"1887_CR28","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","volume":"46","author":"M Kircher","year":"2014","unstructured":"Kircher M, Witten DM, Jain P, O\u2019Roak BJ, Cooper GM, Shendure J (2014) A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46:310\u2013315. \n                    https:\/\/doi.org\/10.1038\/ng.2892","journal-title":"Nat Genet"},{"key":"1887_CR29","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1101\/gad.1767009","volume":"23","author":"MT Knuesel","year":"2009","unstructured":"Knuesel MT, Meyer KD, Bernecky C, Taatjes DJ (2009) The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function. Genes Dev 23:439\u2013451. \n                    https:\/\/doi.org\/10.1101\/gad.1767009","journal-title":"Genes Dev"},{"key":"1887_CR30","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature19057","volume":"536","author":"M Lek","year":"2016","unstructured":"Lek M et al (2016) Analysis of protein-coding genetic variation in 60,706. Hum Nat 536:285\u2013291. \n                    https:\/\/doi.org\/10.1038\/nature19057","journal-title":"Hum Nat"},{"key":"1887_CR31","doi-asserted-by":"publisher","unstructured":"Lelieveld SH et al (2017) Spatial clustering of de novo missense mutations identifies candidate neurodevelopmental disorder-associated genes. Am J Hum Genet 101:478\u2013484. \n                    https:\/\/doi.org\/10.1016\/j.ajhg.2017.08.004","DOI":"10.1016\/j.ajhg.2017.08.004"},{"key":"1887_CR32","unstructured":"Lyons MJ (1993) MED12-Related Disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews((R)). Seattle (WA)"},{"key":"1887_CR33","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.tibs.2005.03.009","volume":"30","author":"S Malik","year":"2005","unstructured":"Malik S, Roeder RG (2005) Dynamic regulation of pol II transcription by the mammalian Mediator complex. Trends Biochem Sci 30:256\u2013263. \n                    https:\/\/doi.org\/10.1016\/j.tibs.2005.03.009","journal-title":"Trends Biochem Sci"},{"key":"1887_CR34","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1136\/jmedgenet-2016-103964","volume":"54","author":"F Martinez","year":"2017","unstructured":"Martinez F, Caro-Llopis A, Rosello M, Oltra S, Mayo S, Monfort S, Orellana C (2017) High diagnostic yield of syndromic intellectual disability by targeted next-generation sequencing. J Med Genet 54:87\u201392. \n                    https:\/\/doi.org\/10.1136\/jmedgenet-2016-103964","journal-title":"J Med Genet"},{"key":"1887_CR35","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/s00439-010-0848-x","volume":"128","author":"A Mukhopadhyay","year":"2010","unstructured":"Mukhopadhyay A et al (2010) CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation. Hum Genet 128:281\u2013291. \n                    https:\/\/doi.org\/10.1007\/s00439-010-0848-x","journal-title":"Hum Genet"},{"key":"1887_CR36","doi-asserted-by":"publisher","first-page":"2843","DOI":"10.1161\/01.CIR.0000103684.77636.CD","volume":"108","author":"N Muncke","year":"2003","unstructured":"Muncke N et al (2003) Missense mutations and gene interruption in PROSIT240, a novel TRAP240-like gene, in patients with congenital heart defect (transposition of the great arteries. Circulation 108:2843\u20132850. \n                    https:\/\/doi.org\/10.1161\/01.CIR.0000103684.77636.CD","journal-title":"Circulation"},{"key":"1887_CR37","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1002\/humu.22450","volume":"34","author":"K Neveling","year":"2013","unstructured":"Neveling K et al (2013) A post-hoc comparison of the utility of sanger sequencing and exome sequencing for the diagnosis of heterogeneous diseases. Hum Mut 34:1721\u20131726. \n                    https:\/\/doi.org\/10.1002\/humu.22450","journal-title":"Hum Mut"},{"key":"1887_CR38","doi-asserted-by":"publisher","first-page":"e1003709","DOI":"10.1371\/journal.pgen.1003709","volume":"9","author":"S Petrovski","year":"2013","unstructured":"Petrovski S, Wang Q, Heinzen EL, Allen AS, Goldstein DB (2013) Genic intolerance to functional variation and the interpretation of personal genomes. PLoS Genet 9:e1003709. \n                    https:\/\/doi.org\/10.1371\/journal.pgen.1003709","journal-title":"PLoS Genet"},{"key":"1887_CR39","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3109\/10409238.2013.840259","volume":"48","author":"ZC Poss","year":"2013","unstructured":"Poss ZC, Ebmeier CC, Taatjes DJ (2013) The Mediator complex and transcription regulation. Crit Rev Biochem Mol Biol 48:575\u2013608. \n                    https:\/\/doi.org\/10.3109\/10409238.2013.840259","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"1887_CR40","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00894-017-3258-3","volume":"23","author":"JW Prokop","year":"2017","unstructured":"Prokop JW, Lazar J, Crapitto G, Smith DC, Worthey EA, Jacob HJ (2017) Molecular modeling in the age of clinical genomics, the enterprise of the next generation. J Mol Model 23:75. \n                    https:\/\/doi.org\/10.1007\/s00894-017-3258-3","journal-title":"J Mol Model"},{"key":"1887_CR41","unstructured":"R Core Team (2013) R: A language and environment for statistical computing \n                    http:\/\/www.r-project.org\n                    \n                  . Vienna A, R Foundation for Statistical Computing"},{"key":"1887_CR42","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/ng1992","volume":"39","author":"H Risheg","year":"2007","unstructured":"Risheg H et al (2007) A recurrent mutation in MED12 leading to R961W causes Opitz\u2013Kaveggia syndrome. Nat Genet 39:451\u2013453. \n                    https:\/\/doi.org\/10.1038\/ng1992","journal-title":"Nat Genet"},{"key":"1887_CR43","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1038\/nn.4524","volume":"20","author":"RK Yuen","year":"2017","unstructured":"Yuen RK et al (2017) Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci 20:602\u2013611. \n                    https:\/\/doi.org\/10.1038\/nn.4524","journal-title":"Nat Neurosci"},{"key":"1887_CR44","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1038\/ng.3050","volume":"46","author":"KE Samocha","year":"2014","unstructured":"Samocha KE et al (2014) A framework for the interpretation of de novo mutation in human disease. Nat Genet 46:944\u2013950. \n                    https:\/\/doi.org\/10.1038\/ng.3050","journal-title":"Nat Genet"},{"key":"1887_CR45","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1136\/jmg.2006.048637","volume":"44","author":"CE Schwartz","year":"2007","unstructured":"Schwartz CE et al (2007) The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene. J Med Genet 44:472\u2013477. \n                    https:\/\/doi.org\/10.1136\/jmg.2006.048637","journal-title":"J Med Genet"},{"key":"1887_CR46","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1002\/humu.22844","volume":"36","author":"N Sobreira","year":"2015","unstructured":"Sobreira N, Schiettecatte F, Valle D, Hamosh A (2015) GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Human Mutation 36:928\u2013930. \n                    https:\/\/doi.org\/10.1002\/humu.22844","journal-title":"Human Mutation"},{"key":"1887_CR47","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1002\/humu.23303","volume":"38","author":"E Sollis","year":"2017","unstructured":"Sollis E et al (2017) Equivalent missense variant in the FOXP2 and FOXP1 transcription factors causes distinct neurodevelopmental disorders. Human mutation 38:1542\u20131554. \n                    https:\/\/doi.org\/10.1002\/humu.23303","journal-title":"Human mutation"},{"key":"1887_CR48","doi-asserted-by":"publisher","unstructured":"Tanaka AJ et al (2015) Mutations in SPATA5 are associated with microcephaly, intellectual disability, seizures, and hearing loss. Am J Human Genetics 97:457\u2013464. \n                    https:\/\/doi.org\/10.1016\/j.ajhg.2015.07.014","DOI":"10.1016\/j.ajhg.2015.07.014"},{"key":"1887_CR49","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/nsmb.2549","volume":"20","author":"KL Tsai","year":"2013","unstructured":"Tsai KL, Sato S, Tomomori-Sato C, Conaway RC, Conaway JW, Asturias FJ (2013) A conserved mediator-CDK8 kinase module association regulates Mediator-RNA polymerase II interaction. Nat Struct Mol Biol 20:611\u2013619. \n                    https:\/\/doi.org\/10.1038\/nsmb.2549","journal-title":"Nat Struct Mol Biol"},{"key":"1887_CR50","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/ejhg.2014.69","volume":"23","author":"MM van Haelst","year":"2015","unstructured":"van Haelst MM, Monroe GR, Duran K, van Binsbergen E, Breur JM, Giltay JC, van Haaften G (2015) Further confirmation of the MED13L haploinsufficiency syndrome. Eur J Hum Genet 23:135\u2013138. \n                    https:\/\/doi.org\/10.1038\/ejhg.2014.69","journal-title":"Eur J Hum Genet"},{"key":"1887_CR51","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrg3999","volume":"17","author":"LE Vissers","year":"2016","unstructured":"Vissers LE, Gilissen C, Veltman JA (2016) Genetic studies in intellectual disability and related disorders. Nat Rev Genet 17:9\u201318. \n                    https:\/\/doi.org\/10.1038\/nrg3999","journal-title":"Nat Rev Genet"},{"key":"1887_CR52","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.ajhg.2013.01.007","volume":"92","author":"AT Vulto-van Silfhout","year":"2013","unstructured":"Vulto-van Silfhout AT et al (2013) Mutations in MED12 cause X-linked Ohdo syndrome. Am J Human Genetics 92:401\u2013406. \n                    https:\/\/doi.org\/10.1016\/j.ajhg.2013.01.007","journal-title":"Am J Human Genetics"}],"container-title":["Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00439-018-1887-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-018-1887-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00439-018-1887-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T13:45:36Z","timestamp":1589636736000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00439-018-1887-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["1887"],"URL":"https:\/\/doi.org\/10.1007\/s00439-018-1887-y","relation":{},"ISSN":["0340-6717","1432-1203"],"issn-type":[{"value":"0340-6717","type":"print"},{"value":"1432-1203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5]]},"assertion":[{"value":"29 December 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"H.M., R.P. and A.C. are employees of GeneDx, Inc., a wholly owned subsidiary of OPKO Health, Inc. The other authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants"}},{"value":"Informed consent was obtained from all individual participants included in the study. Additional informed consent was obtained from all individual participants for whom identifying information is included in this article.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}