{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:32:42Z","timestamp":1790760762873,"version":"4.1.0"},"reference-count":38,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mol Syndromol"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:p>Objectives: Clefts of the lip, alveolus and\/or palate (CLA\/P) are the most common craniofacial congenital malformations in humans. These oral clefts can be divided into non-syndromic (isolated) and syndromic forms. Many cleft-related syndromes are clinically variable and genetically heterogeneous, making it challenging to distinguish syndromic from non-syndromic cases. Recognition of syndromic\/genetic causes is important for personalized tailored care, identification of (unrecognized) comorbidities, and accurate genetic counseling. Therefore, next generation sequencing (NGS)-based targeted gene panel testing is increasingly implemented in diagnostics of CLA\/P patients. In this retrospective study, we assess the yield of NGS gene panel testing in a cohort of CLA\/P cases. Methods: Whole exome sequencing (WES) followed by variant detection and interpretation in an a priori selected set of genes associated with CLA\/P phenotypes was performed in 212 unrelated CLA\/P patients after genetic counseling between 2015 and 2020. Medical records including family history and results of additional genetic tests were evaluated. Results: In 24 CLA\/P cases (11.3%), a pathogenic genetic variant was identified. Twenty out of these 24 had a genetic syndrome requiring specific monitoring and follow-up. Six of these 24 cases (25%) were presumed to be isolated CLA\/P cases prior to testing, corresponding to 2.8% of the total cohort. In eight CLA\/P cases (3.8%) without a diagnosis after NGS-based gene panel testing, a molecular diagnosis was established by additional genetic analyses (e.g., SNP array, single gene testing, trio WES). Conclusion: This study illustrates NGS-based gene panel testing is a powerful diagnostic tool in the diagnostic workup of CLA\/P patients. Also, in apparently isolated cases and non-familial cases, a genetic diagnosis can be identified. Early diagnosis facilitates personalized care for patients and accurate genetic counseling of their families. <\/jats:p>","DOI":"10.1159\/000530256","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T13:02:31Z","timestamp":1691413351000},"page":"270-282","source":"Crossref","is-referenced-by-count":9,"title":["Diagnostic Gene Panel Testing in (Non)-Syndromic Patients with Cleft Lip, Alveolus and\/or Palate in the Netherlands"],"prefix":"10.1159","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-3801","authenticated-orcid":false,"given":"Lisca Florence","family":"Wurfbain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Lucia","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francisca","family":"van 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