{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T02:10:15Z","timestamp":1762049415608,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research (NIDCR)\/National Institutes of Health (NIH)","doi-asserted-by":"publisher","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"US Centers for Disease Control and Prevention","doi-asserted-by":"publisher","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}],"id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIDCR\/NIH","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}]},{"name":"Wellcome Investigator Award","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}]},{"name":"Intramural Research Program, National Institute of Child Health and Human Development, NIH","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}]},{"name":"Center for Inherited Disease Research (CIDR)","award":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"],"award-info":[{"award-number":["R01 DE016886","U01 DD001223","R01 R01DE018227","102731","HHSN275201100001I","HHSN27500005","HHSN268200782096C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Craniosynostosis (CS) is a major birth defect in which one or more skull sutures fuse prematurely. We previously performed a genome-wide association study (GWAS) for sagittal non-syndromic CS (sNCS), identifying associations downstream from BMP2 on 20p12.3 and intronic to BBS9 on 7p14.3; analyses of imputed variants in DLG1 on 3q29 were also genome-wide significant. We followed this work with a GWAS for metopic non-syndromic NCS (mNCS), discovering a significant association intronic to BMP7 on 20q13.31. In the current study, we sequenced the associated regions on 3q29, 7p14.3, and 20p12.3, including two candidate genes (BMP2 and BMPER) near some of these regions in 83 sNCS child-parent trios, and sequenced regions on 7p14.3 and 20q13.2-q13.32 in 80 mNCS child-parent trios. These child-parent trios were selected from the original GWAS cohorts if the probands carried at least one copy of the top associated GWAS variant (rs1884302 C allele for sNCS; rs6127972 T allele for mNCS). Many of the variants sequenced in these targeted regions are strongly predicted to be within binding sites for transcription factors involved in craniofacial development or bone morphogenesis. Variants enriched in more than one trio and predicted to be damaging to gene function are prioritized for functional studies.<\/jats:p>","DOI":"10.3390\/genes13050816","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T08:26:35Z","timestamp":1651566395000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis"],"prefix":"10.3390","volume":"13","author":[{"given":"Cristina M.","family":"Justice","sequence":"first","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institute of Health (NIH), Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony M.","family":"Musolf","sequence":"additional","affiliation":[{"name":"Statistical Genetics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institute of Health (NIH), Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Araceli","family":"Cuellar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis, Sacramento, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-4936","authenticated-orcid":false,"given":"Wanda","family":"Lattanzi","sequence":"additional","affiliation":[{"name":"Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil","family":"Simeonov","sequence":"additional","affiliation":[{"name":"Pediatric Clinic, Alexandrovska University Hospital, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1437-1393","authenticated-orcid":false,"given":"Radka","family":"Kaneva","sequence":"additional","affiliation":[{"name":"Molecular Medicine Center, Department of Medical Chemistry and Biochemistry, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Paschall","sequence":"additional","affiliation":[{"name":"Bioinformatics Core, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institute of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Seattle Children\u2019s Craniofacial Center, Center of Developmental Biology and Regenerative Medicine and Division of Craniofacial Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew O. M.","family":"Wilkie","sequence":"additional","affiliation":[{"name":"MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK"},{"name":"Oxford Centre for Genomic Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DS, UK"},{"name":"Craniofacial Unit, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander F.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institute of Health (NIH), Baltimore, MD 21224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-9984","authenticated-orcid":false,"given":"Paul A.","family":"Romitti","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeon A.","family":"Boyadjiev","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis, Sacramento, CA 95616, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/ajmg.a.32208","article-title":"A population-based study of craniosynostosis in metropolitan atlanta, 1989\u20132003","volume":"146A","author":"Boulet","year":"2008","journal-title":"Am. 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