{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T08:40:33Z","timestamp":1782981633796,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T00:00:00Z","timestamp":1715212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Next\u2010generation phenotyping (NGP) can be used to compute the similarity of dysmorphic patients to known syndromic diseases. So far, the technology has been evaluated in variant prioritization and classification, providing evidence for pathogenicity if the phenotype matched with other patients with a confirmed molecular diagnosis. In a Nigerian cohort of individuals with facial dysmorphism, we used the NGP tool GestaltMatcher to screen portraits prior to genetic testing and subjected individuals with high similarity scores to exome sequencing (ES). Here, we report on two individuals with global developmental delay, pulmonary artery stenosis, and genital and limb malformations for whom GestaltMatcher yielded Cornelia de Lange syndrome (CdLS) as the top hit. ES revealed a known pathogenic nonsense variant, NM_133433.4: c.598C&gt;T; p.(Gln200*), as well as a novel frameshift variant c.7948dup; p.(Ile2650Asnfs*11) in\n                    <jats:italic>NIPBL<\/jats:italic>\n                    . Our results suggest that NGP can be used as a screening tool and thresholds could be defined for achieving high diagnostic yields in ES. Training the artificial intelligence (AI) with additional cases of the same ethnicity might further increase the positive predictive value of GestaltMatcher.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63641","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T01:23:52Z","timestamp":1715304232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Next\u2010generation phenotyping in Nigerian children with Cornelia de Lange syndrome"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7268-1567","authenticated-orcid":false,"given":"Annabelle","family":"Arlt","sequence":"first","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0366-0533","authenticated-orcid":false,"given":"Alexej","family":"Knaus","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3828-4419","authenticated-orcid":false,"given":"Tzung\u2010Chien","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3752-1275","authenticated-orcid":false,"given":"Hannah","family":"Klinkhammer","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"},{"name":"Institute for Medical Biometry, Informatics and Epidemiology, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2944-6880","authenticated-orcid":false,"given":"Meghna Ahuja","family":"Bhasin","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4592-3979","authenticated-orcid":false,"given":"Alexander","family":"Hustinx","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4463-3067","authenticated-orcid":false,"given":"Shahida","family":"Moosa","sequence":"additional","affiliation":[{"name":"Division of Molecular Biology and Human Genetics Stellenbosch University and Medical Genetics, Tygerberg Hospital  Cape Town South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3194-8625","authenticated-orcid":false,"given":"Peter","family":"Krawitz","sequence":"additional","affiliation":[{"name":"Institute for Genomic Statistics and Bioinformatics, University Hospital Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8257-1864","authenticated-orcid":false,"given":"Ekanem","family":"Ekure","sequence":"additional","affiliation":[{"name":"Faculty of Clinical Sciences, Department of Pediatrics College of Medicine, University of Lagos  Lagos Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,9]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61033"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.32056"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa241"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.906"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0566-2"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-01010-x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","unstructured":"Hustinx A. Hellmann F. S\u00fcmer \u00d6. Javanmardi B. Andr\u00e9 E. Krawitz P. &Hsieh T.\u2010C.(2022).Improving deep facial phenotyping for ultra\u2010rare disorder verification using model ensembles.ArXiv [Cs.CV]. arXiv.https:\/\/openaccess.thecvf.com\/content\/WACV2023\/html\/Hustinx_Improving_Deep_Facial_Phenotyping_for_Ultra-Rare_Disorder_Verification_Using_Model_WACV_2023_paper.html","DOI":"10.1109\/WACV56688.2023.00499"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"issue":"2","key":"e_1_2_13_10_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1515\/medgen-2023-2014","article-title":"The future role of facial image analysis in ACMG classification guidelines","volume":"35","author":"Lesmann H.","year":"2023","journal-title":"Medizinische Genetik: Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.06.06.23290887"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22430"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.3"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1779"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nargab\/lqab078"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33441"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.04.19.23288824"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1109\/ICCV.2017.74"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.210"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T11:25:20Z","timestamp":1728473120000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,9]]},"references-count":18,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/ajmg.a.63641"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63641","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.02.15.24302695","asserted-by":"object"}]},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,9]]},"assertion":[{"value":"2024-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63641"}}