{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T16:08:20Z","timestamp":1780070900845,"version":"3.54.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2022T150445"],"award-info":[{"award-number":["2022T150445"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the <jats:italic>DHODH<\/jats:italic> gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup\u2010shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a prenatal case with multiple orofacial\u2010limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole\u2010exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in <jats:italic>DHODH<\/jats:italic>, consisting of two variants: exon(1\u20103)del and c.819\u2009+\u20095G\u2009&gt;\u2009A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819\u2009+\u20095G\u2009&gt;\u2009A variant would lead to an exon skipping in mRNA splicing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings provided with the first exonic deletion and first splice site variant in <jats:italic>DHODH<\/jats:italic>, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2186","type":"journal-article","created":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T12:15:00Z","timestamp":1682856900000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Assessment of a novel variation in <i>DHODH<\/i> gene causing Miller syndrome: The first report in Chinese 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