{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T08:28:50Z","timestamp":1787905730657,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T00:00:00Z","timestamp":1632787200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cranio\u2010lenticulo\u2010sutural dysplasia (CLSD; MIM 607812) is a rare or underdiagnosed condition, as only two families have been reported. The original family (Boyadjiev et al.,<jats:italic>Human Genetics<\/jats:italic>, 2003, 113, 1\u20139 and Boyadjiev et al.,<jats:italic>Nature Genetics<\/jats:italic>, 2006, 38, 1192\u20131197) showed recessive inheritance of the condition with a biallelic<jats:italic>SEC23A<\/jats:italic>missense variant in affected individuals. In contrast, another child with sporadic CLSD had a monoallelic<jats:italic>SEC23A<\/jats:italic>variant inherited from the reportedly unaffected father (Boyadjiev et al.,<jats:italic>Clinical Genetics<\/jats:italic>, 2011, 80, 169\u2013176), raising questions on possible digenism. Here, we report a 2\u2010month\u2010old boy seen because of large fontanels with wide cranial sutures, a large forehead, hypertelorism, a thin nose, a high arched palate, and micrognathia. His mother was clinically unremarkable, while his father had a history of large fontanels in infancy who had closed only around age 10\u2009years; he also had a large forehead, hypertelorism, a thin, beaked nose and was operated for bilateral glaucoma with exfoliation of the lens capsule. Trio genome sequencing and familial segregation revealed a monoallelic c.1795G\u2009&gt;\u2009A transition in<jats:italic>SEC23A<\/jats:italic>that was de novo in the father and transmitted to the proband. The variant predicts a nonconservative substitution (p.E599K) in an ultra\u2010conserved residue that is seen in 3D models of yeast SEC23 to be involved in direct binding between SEC23 and SAR1 subunits of the coat protein complex II coat. This observation confirms the link between<jats:italic>SEC23A<\/jats:italic>variants and CLSD but suggests that in addition to the recessive inheritance described in the original family,<jats:italic>SEC23A<\/jats:italic>variants may result in dominant inheritance of CLSD, possibly by a dominant\u2010negative disruptive effect on the SEC23 multimer.<\/jats:p>","DOI":"10.1002\/ajmg.a.62506","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T07:31:45Z","timestamp":1632814305000},"page":"319-325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A monoallelic<scp><i>SEC23A<\/i><\/scp>variant<scp>E599K<\/scp>associated with<scp>cranio\u2010lenticulo\u2010sutural<\/scp>dysplasia"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2711-0480","authenticated-orcid":false,"given":"Katarina","family":"Cisarova","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine Lausanne University Hospital and University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7684-3982","authenticated-orcid":false,"given":"Livia","family":"Garavelli","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Azienda USL\u2010IRCCS of Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-7854","authenticated-orcid":false,"given":"Stefano Giuseppe","family":"Caraffi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Azienda USL\u2010IRCCS of Reggio Emilia Reggio Emilia 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Trimarchi","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit Azienda USL\u2010IRCCS of Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Neri","sequence":"additional","affiliation":[{"name":"Ophthalmology Unit, Department of Surgery Azienda USL\u2010IRCCS of Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Belinda","family":"Campos\u2010Xavier","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Lausanne University Hospital and University of Lausanne Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3543-7531","authenticated-orcid":false,"given":"Andrea","family":"Superti\u2010Furga","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Lausanne 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