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Here, we have studied the prevalence and spectrum of genetic alterations associated with coronal suture closure in 100 Scandinavian patients treated at a single craniofacial unit. All patients were phenotypically assessed and analyzed with a custom\u2010designed 63 gene NGS\u2010panel. Most cases (78%) were syndromic forms of CS. Pathogenic and likely pathogenic variants explaining the phenotype were found in 80% of the families with syndromic CS and in 14% of those with nonsyndromic CS. Sixty\u2010five percent of the families had mutations in the CS core genes <jats:italic>FGFR2<\/jats:italic>, <jats:italic>TWIST1<\/jats:italic>, <jats:italic>FGFR3<\/jats:italic>, <jats:italic>TCF12<\/jats:italic>, <jats:italic>EFNB1<\/jats:italic>, <jats:italic>FGFR1<\/jats:italic>, and <jats:italic>POR<\/jats:italic>. Five novel pathogenic\/likely pathogenic variants in <jats:italic>TWIST1<\/jats:italic>, <jats:italic>TCF12<\/jats:italic>, and <jats:italic>EFNB1<\/jats:italic> were identified. We also found novel variants in <jats:italic>SPECC1L<\/jats:italic>, <jats:italic>IGF1R<\/jats:italic>, and <jats:italic>CYP26B1<\/jats:italic> with a possible modulator phenotypic effect. Our findings demonstrate that NGS targeted sequencing is a powerful tool to detect pathogenic mutations in patients with coronal CS and further emphasize the importance of thorough assessment of the patient's phenotype for reliable interpretation of the molecular findings. This is particularly important in patients with complex phenotypes and rare forms of CS.<\/jats:p>","DOI":"10.1002\/ajmg.a.61427","type":"journal-article","created":{"date-parts":[[2019,12,14]],"date-time":"2019-12-14T11:04:11Z","timestamp":1576321451000},"page":"348-356","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["NGS targeted screening of 100 Scandinavian patients with coronal synostosis"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7518-1294","authenticated-orcid":false,"given":"Alexandra","family":"Topa","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Clinical Genetics and Genomics Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rohlin","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias K.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Pathology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-1392","authenticated-orcid":false,"given":"Andr\u00e9","family":"Fehr","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Pathology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lovisa","family":"Lovmar","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Genomics Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6ran","family":"Stenman","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"},{"name":"Department of Pathology Sahlgrenska University Hospital  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"K\u00f6lby","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Sahlgrenska Academy, University of Gothenburg  Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37259"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2018.11.022"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37217"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/13816810.2012.710707"},{"key":"e_1_2_8_6_1","volume-title":"Craniosynostosis: Diagnosis, evaluation, and management","author":"Cohen M. 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