{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:01:34Z","timestamp":1790416894891,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["EG110\/15-1"],"award-info":[{"award-number":["EG110\/15-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Projekt DEAL"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>\n                      We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21\/75 patients a disease-causing variant could be identified among them variants in known SRS genes (\n                      <jats:italic>IGF2, PLAG1, HMGA2<\/jats:italic>\n                      ). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-021-01683-x","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T02:03:21Z","timestamp":1611281001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver\u2013Russell syndrome"],"prefix":"10.1186","volume":"16","author":[{"given":"Robert","family":"Meyer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Begemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Thomas","family":"H\u00fcbner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Dey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alma","family":"Kuechler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdeldin","family":"Elgizouli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laima","family":"Ambrozaityte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birute","family":"Burnyte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Schr\u00f6der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Kenawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kroisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Demuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyorgy","family":"Fekete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Opladen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Elbracht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8419-0264","authenticated-orcid":false,"given":"Thomas","family":"Eggermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"issue":"7","key":"1683_CR1","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1136\/jmedgenet-2014-102979","volume":"52","author":"S Azzi","year":"2015","unstructured":"Azzi S, Salem J, Thibaud N, Chantot-Bastaraud S, Lieber E, Netchine I, Harbison MD. A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome. J Med Genet. 2015;52(7):446\u201353.","journal-title":"J Med Genet"},{"issue":"2","key":"1683_CR2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/nrendo.2016.138","volume":"13","author":"EL Wakeling","year":"2017","unstructured":"Wakeling EL, Brioude F, Lokulo-Sodipe O, O\u2019Connell SM, Salem J, Bliek J, Canton AP, Chrzanowska KH, Davies JH, Dias RP, Dubern B, Elbracht M, Giabicani E, Grimberg A, Gronskov K, Hokken-Koelega AC, Jorge AA, Kagami M, Linglart A, Maghnie M, Mohnike K, Monk D, Moore GE, Murray PG, Ogata T, Petit IO, Russo S, Said E, Toumba M, Tumer Z, Binder G, Eggermann T, Harbison MD, Temple IK, Mackay DJ, Netchine I. Diagnosis and management of Silver\u2013Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105\u201324.","journal-title":"Nat Rev Endocrinol"},{"key":"1683_CR3","doi-asserted-by":"crossref","unstructured":"Geoffron S, Abi Habib W, Chantot-Bastaraud S, Dubern B, Steunou V, Azzi S, Afenjar A, Busa T, Pinheiro Canton A, Chalouhi C, Dufourg MN, Esteva B, Fradin M, Genevieve D, Heide S, Isidor B, Linglart A, Morice Picard F, Naud-Saudreau C, Oliver Petit I, Philip N, Pienkowski C, Rio M, Rossignol S, Tauber M, Thevenon J, Vu-Hong TA, Harbison MD, Salem J, Brioude F, Netchine I, Giabicani E. Chromosome 14q32.2 imprinted region disruption as an alternative molecular diagnosis of Silver\u2013Russell syndrome. J Clin Endocrinol Metab. 2018;103(7):2436\u201346.","DOI":"10.1210\/jc.2017-02152"},{"issue":"3","key":"1683_CR4","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/humu.23382","volume":"39","author":"Z Tumer","year":"2018","unstructured":"Tumer Z, Lopez-Hernandez JA, Netchine I, Elbracht M, Gronskov K, Gede LB, Sachwitz J, den Dunnen JT, Eggermann T. Structural and sequence variants in patients with Silver\u2013Russell syndrome or similar features-Curation of a disease database. Hum Mutat. 2018;39(3):345\u201364.","journal-title":"Hum Mutat"},{"issue":"12","key":"1683_CR5","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1136\/jmedgenet-2013-101691","volume":"50","author":"F Brioude","year":"2013","unstructured":"Brioude F, Oliver-Petit I, Blaise A, Praz F, Rossignol S, Le Jule M, Thibaud N, Faussat AM, Tauber M, Le Bouc Y, Netchine I. CDKN1C mutation affecting the PCNA-binding domain as a cause of familial Russell\u2013Silver syndrome. J Med Genet. 2013;50(12):823\u201330.","journal-title":"J Med Genet"},{"issue":"4","key":"1683_CR6","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1056\/NEJMoa1415227","volume":"373","author":"M Begemann","year":"2015","unstructured":"Begemann M, Zirn B, Santen G, Wirthgen E, Soellner L, Buttel HM, Schweizer R, van Workum W, Binder G, Eggermann T. Paternally inherited IGF2 mutation and growth restriction. N Engl J Med. 2015;373(4):349\u201356.","journal-title":"N Engl J Med"},{"key":"1683_CR7","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.jpeds.2017.04.018","volume":"187","author":"R Meyer","year":"2017","unstructured":"Meyer R, Soellner L, Begemann M, Dicks S, Fekete G, Rahner N, Zerres K, Elbracht M, Eggermann T. Targeted next generation sequencing approach in patients referred for Silver\u2013Russell syndrome testing increases the mutation detection rate and provides decisive information for clinical management. J Pediatr. 2017;187:206\u201312.","journal-title":"J Pediatr"},{"key":"1683_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.mcp.2018.12.007","volume":"44","author":"L Neuheuser","year":"2019","unstructured":"Neuheuser L, Meyer R, Begemann M, Elbracht M, Eggermann T. Next generation sequencing and imprinting disorders: current applications and future perspectives: lessons from Silver\u2013Russell syndrome. Mol Cell Probes. 2019;44:1\u20137.","journal-title":"Mol Cell Probes"},{"issue":"5","key":"1683_CR9","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, Committee ALQA. 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. 2015;17(5):405\u201324.","journal-title":"Genet Med"},{"issue":"10","key":"1683_CR10","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1038\/ejhg.2016.45","volume":"24","author":"K Eggermann","year":"2016","unstructured":"Eggermann K, Bliek J, Brioude F, Algar E, Buiting K, Russo S, Tumer Z, Monk D, Moore G, Antoniadi T, Macdonald F, Netchine I, Lombardi P, Soellner L, Begemann M, Prawitt D, Maher ER, Mannens M, Riccio A, Weksberg R, Lapunzina P, Gronskov K, Mackay DJ, Eggermann T. EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver\u2013Russell and Beckwith\u2013Wiedemann syndrome. Eur J Hum Genet. 2016;24(10):1377\u201387.","journal-title":"Eur J Hum Genet"},{"issue":"24","key":"1683_CR11","doi-asserted-by":"publisher","first-page":"4724","DOI":"10.1093\/hmg\/ddp435","volume":"18","author":"S Azzi","year":"2009","unstructured":"Azzi S, Rossignol S, Steunou V, Sas T, Thibaud N, Danton F, Le Jule M, Heinrichs C, Cabrol S, Gicquel C, Le Bouc Y, Netchine I. Multilocus methylation analysis in a large cohort of 11p15-related foetal growth disorders (Russell Silver and Beckwith Wiedemann syndromes) reveals simultaneous loss of methylation at paternal and maternal imprinted loci. Hum Mol Genet. 2009;18(24):4724\u201333.","journal-title":"Hum Mol Genet"},{"key":"1683_CR12","doi-asserted-by":"crossref","unstructured":"Masunaga Y, Inoue T, Yamoto K, Fujisawa Y, Sato Y, Kawashima-Sonoyama Y, Morisada N, Iijima K, Ohata Y, Namba N, Suzumura H, Kuribayashi R, Yamaguchi Y, Yoshihashi H, Fukami M, Saitsu H, Kagami M, Ogata T. IGF2 Mutations. J Clin Endocrinol Metab. 2020;105(1).","DOI":"10.1210\/clinem\/dgz034"},{"issue":"4","key":"1683_CR13","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/nrendo.2017.166","volume":"14","author":"F Brioude","year":"2018","unstructured":"Brioude F, Kalish JM, Mussa A, Foster AC, Bliek J, Ferrero GB, Boonen SE, Cole T, Baker R, Bertoletti M, Cocchi G, Coze C, De Pellegrin M, Hussain K, Ibrahim A, Kilby MD, Krajewska-Walasek M, Kratz CP, Ladusans EJ, Lapunzina P, Le Bouc Y, Maas SM, Macdonald F, Ounap K, Peruzzi L, Rossignol S, Russo S, Shipster C, Skorka A, Tatton-Brown K, Tenorio J, Tortora C, Gronskov K, Netchine I, Hennekam RC, Prawitt D, Tumer Z, Eggermann T, Mackay DJG, Riccio A, Maher ER. Expert consensus document: clinical and molecular diagnosis, screening and management of Beckwith\u2013Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol. 2018;14(4):229\u201349.","journal-title":"Nat Rev Endocrinol"},{"issue":"2","key":"1683_CR14","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1038\/gim.2017.105","volume":"20","author":"W Abi Habib","year":"2018","unstructured":"Abi Habib W, Brioude F, Edouard T, Bennett JT, Lienhardt-Roussie A, Tixier F, Salem J, Yuen T, Azzi S, Le Bouc Y, Harbison MD, Netchine I. Genetic disruption of the oncogenic HMGA2-PLAG1-IGF2 pathway causes fetal growth restriction. Genet Med. 2018;20(2):250\u20138.","journal-title":"Genet Med"},{"issue":"6","key":"1683_CR15","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1530\/EJE-17-0453","volume":"177","author":"L Shapiro","year":"2017","unstructured":"Shapiro L, Chatterjee S, Ramadan DG, Davies KM, Savage MO, Metherell LA, Storr HL. Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity. Eur J Endocrinol. 2017;177(6):485\u2013501.","journal-title":"Eur J Endocrinol"},{"issue":"6","key":"1683_CR16","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1038\/gim.2017.159","volume":"20","author":"NN Hauer","year":"2018","unstructured":"Hauer NN, Popp B, Schoeller E, Schuhmann S, Heath KE, Hisado-Oliva A, Klinger P, Kraus C, Trautmann U, Zenker M, Zweier C, Wiesener A, Abou Jamra R, Kunstmann E, Wieczorek D, Uebe S, Ferrazzi F, Buttner C, Ekici AB, Rauch A, Sticht H, Dorr HG, Reis A, Thiel CT. Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. Genet Med. 2018;20(6):630\u20138.","journal-title":"Genet Med"},{"issue":"7","key":"1683_CR17","doi-asserted-by":"publisher","first-page":"2401","DOI":"10.1210\/clinem\/dgaa273","volume":"105","author":"CT H\u00fcbner","year":"2020","unstructured":"H\u00fcbner CT, Meyer R, Kenawy A, Ambrozaityte L, Matuleviciene A, Kraft F, Begemann M, Elbracht M, Eggermann T. HMGA2 variants in Silver-Russell syndrome: homozygous and heterozygous occurrence. J Clin Endocrinol Metab. 2020;105(7):2401\u20137.","journal-title":"J Clin Endocrinol Metab"},{"key":"1683_CR18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.gene.2018.04.027","volume":"663","author":"GS Leszinski","year":"2018","unstructured":"Leszinski GS, Warncke K, Hoefele J, Wagner M. A case report and review of the literature indicate that HMGA2 should be added as a disease gene for Silver-Russell syndrome. Gene. 2018;663:110\u20134.","journal-title":"Gene"},{"issue":"3","key":"1683_CR19","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1136\/jmedgenet-2019-106328","volume":"57","author":"E Giabicani","year":"2020","unstructured":"Giabicani E, Willems M, Steunou V, Chantot-Bastaraud S, Thibaud N, Abi Habib W, Azzi S, Lam B, Berard L, Bony-Trifunovic H, Brachet C, Brischoux-Boucher E, Caldagues E, Coutant R, Cuvelier ML, Gelwane G, Guemas I, Houang M, Isidor B, Jeandel C, Lespinasse J, Naud-Saudreau C, Jesuran-Perelroizen M, Perrin L, Piard J, Sechter C, Souchon PF, Storey C, Thomas D, Le Bouc Y, Rossignol S, Netchine I, Brioude F. Increasing knowledge in IGF1R defects: lessons from 35 new patients. J Med Genet. 2020;57(3):160\u20138.","journal-title":"J Med Genet"},{"key":"1683_CR20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s13023-015-0322-x","volume":"10","author":"SA de Munnik","year":"2015","unstructured":"de Munnik SA, Hoefsloot EH, Roukema J, Schoots J, Knoers NV, Brunner HG, Jackson AP, Bongers EM. Meier-Gorlin syndrome. Orphanet J Rare Dis. 2015;10:114.","journal-title":"Orphanet J Rare Dis"},{"issue":"6","key":"1683_CR21","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1002\/ajmg.a.34009","volume":"155A","author":"NA Akawi","year":"2011","unstructured":"Akawi NA, Ali BR, Hamamy H, Al-Hadidy A, Al-Gazali L. Is autosomal recessive Silver\u2013Russel syndrome a separate entity or is it part of the 3-M syndrome spectrum? Am J Med Genet A. 2011;155A(6):1236\u201345.","journal-title":"Am J Med Genet A"},{"key":"1683_CR22","doi-asserted-by":"crossref","unstructured":"Kondo Y, Fu J, Wang H, Hoover C, McDaniel JM, Steet R, Patra D, Song J, Pollard L, Cathey S, Yago T, Wiley G, Macwana S, Guthridge J, McGee S, Li S, Griffin C, Furukawa K, James JA, Ruan C, McEver RP, Wierenga KJ, Gaffney PM, Xia L. Site-1 protease deficiency causes human skeletal dysplasia due to defective inter-organelle protein trafficking. JCI Insight. 2018;3(14).","DOI":"10.1172\/jci.insight.121596"},{"issue":"6","key":"1683_CR23","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1203\/01.pdr.0000183661.81772.f8","volume":"58","author":"K Wimmer","year":"2005","unstructured":"Wimmer K, Decker M, Mayatepek E, Beiglbock H, Eggermann T, Kehrer-Sawatzki H, Fonatsch C, Rosenbaum T. Silver\u2013Russell syndrome-like features in a patient carrying a novel NF1 mutation. Pediatr Res. 2005;58(6):1265\u20138.","journal-title":"Pediatr Res"},{"key":"1683_CR24","doi-asserted-by":"crossref","unstructured":"Eggermann T, Elbracht M, Kurth I, Juul A, Johannsen TH, Netchine I, Mastorakos G, Johannsson G, Musholt TJ, Zenker M, Prawitt D, Pereira AM, Hiort O, European Reference Network on Rare Endocrine C. Genetic testing in inherited endocrine disorders: joint position paper of the European reference network on rare endocrine conditions (Endo-ERN). Orphanet J Rare Dis. 2020;15(1):144.","DOI":"10.1186\/s13023-020-01420-w"},{"issue":"11","key":"1683_CR25","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1002\/ajmg.a.61833","volume":"182","author":"R Meyer","year":"2020","unstructured":"Meyer R, Elbracht M, Opladen T, Eggermann T. Patient with an autosomal-recessive MBTPS1-linked phenotype and clinical features of Silver-Russell syndrome. Am J Med Genet Part A. 2020;182(11):2727\u201330.","journal-title":"Am J Med Genet Part A."},{"issue":"4","key":"1683_CR26","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/cge.13819","volume":"98","author":"R Meyer","year":"2020","unstructured":"Meyer R, Begemann M, Demuth S, Kraft F, Dey D, Sch\u00fcler H, Busse S, H\u00e4usler M, Zerres K, Kurth I, Eggermann T, Elbracht M. Inherited cases of CNOT3-associated intellectual developmental disorder with speech delay, autism, and dysmorphic facies. Clin Genet. 2020;98(4):408\u201312.","journal-title":"Clin Genet"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01683-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13023-021-01683-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-021-01683-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T02:18:35Z","timestamp":1611281915000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-01683-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,22]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1683"],"URL":"https:\/\/doi.org\/10.1186\/s13023-021-01683-x","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,22]]},"assertion":[{"value":"3 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the ethical committee of the Medical Faculty of the RWTH Aachen (EK303-18).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All participants gave their informed content for participation in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"42"}}