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Genes associated with these syndromes encode proteins that have crucial roles in DNA replication or in other critical steps of the cell cycle that link DNA replication to cell division. We identified four unrelated families with five affected individuals having biallelic or de novo variants in <jats:italic>DONSON<\/jats:italic> presenting with a core phenotype of severe short stature (z score\u2009&lt;\u2009\u22123 <jats:italic>SD<\/jats:italic>), additional skeletal abnormalities, and microcephaly. Two apparently unrelated families with identical homozygous c.631C\u2009&gt;\u2009T p.(Arg211Cys) variant had clinical features typical of Meier\u2010Gorlin syndrome (MGS), while two siblings with compound heterozygous c.346delG p.(Asp116Ile*62) and c.1349A\u2009&gt;\u2009G p.(Lys450Arg) variants presented with Seckel\u2010like phenotype. We also identified a de novo c.683G\u2009&gt;\u2009T p.(Trp228Leu) variant in <jats:italic>DONSON<\/jats:italic> in a patient with prominent micrognathia, short stature and hypoplastic femur and tibia, clinically diagnosed with Femoral\u2010Facial syndrome (FFS, OMIM 134780). Biallelic variants in <jats:italic>DONSON<\/jats:italic> have been recently described in individuals with microcephalic dwarfism. These studies also demonstrated that DONSON has an essential conserved role in the cell cycle. Here we describe novel biallelic and de novo variants that are associated with MGS, Seckel\u2010like phenotype and FFS, the last of which has not been associated with any disease gene to date.<\/jats:p>","DOI":"10.1002\/ajmg.a.61315","type":"journal-article","created":{"date-parts":[[2019,8,13]],"date-time":"2019-08-13T11:55:15Z","timestamp":1565697315000},"page":"2056-2066","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Biallelic and <i>De Novo<\/i> Variants in <i>DONSON<\/i> Reveal a Clinical Spectrum of Cell Cycle\u2010opathies with Microcephaly, Dwarfism and Skeletal Abnormalities"],"prefix":"10.1002","volume":"179","author":[{"given":"Ender","family":"Karaca","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret","family":"Bostwick","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Hospital Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alper","family":"Gezdirici","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Kanuni Sultan Suleyman Training and Research Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gozde","family":"Yesil","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Bezmialem University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Coban Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavuz","family":"Bayram","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederike L.","family":"Harms","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Meinecke","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Alawi","sequence":"additional","affiliation":[{"name":"Bioinformatics Service Facility University Medical Center Hamburg\u2013Eppendorf  Hamburg Germany"},{"name":"Center for Bioinformatics University of Hamburg  Hamburg Germany"},{"name":"Heinrich Pette Institute Leibniz Institute for Experimental Virology  Virus Genomics, Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos A.","family":"Bacino","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas"},{"name":"Texas Children's Hospital Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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