{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:02:48Z","timestamp":1792612968730,"version":"4.5.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the detection rate of exome sequencing (ES) in fetuses diagnosed as skeletal abnormalities (SKA) with normal karyotype or chromosomal microarray analysis (CMA) results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted electronic searches in four databases, focusing on studies involving ES in fetuses with SKA. Additional detection rate of ES compared to karyotype\/CMA was calculated, followed by a meta-analysis. Subgroup analyses explored the influence of fetal phenotype on diagnostic outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From 2,393 studies, 21 reports covering 476 fetuses were analyzed. Key findings include: (1) an additional detection rate of ES of 63.2% (Risk Difference (RD), 0.68 [95% CI, 0.60\u20130.76], p &amp;lt; 0.00001); (2) identification of 76 genes across 304 types of variants, with <jats:italic>FGFR3<\/jats:italic>, <jats:italic>COL1A1<\/jats:italic>, <jats:italic>COL1A2<\/jats:italic>, and <jats:italic>COL2A1<\/jats:italic> being prevalent; (3) lower detection rates in fetuses with isolated short long bones compared to non-isolated conditions, though not significantly different (p = 0.35); (4) higher detection rates in subgroups with abnormal ossification, small chest, suspected long bone fractures or angulations, and skull abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The meta-analysis indicates that genetic variation significantly contributes to fetal SKA, primarily due to single-gene variants. Consequently, ES should be used in the prenatal diagnosis of SKA fetuses in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fgene.2025.1502538","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T13:23:14Z","timestamp":1749648194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exome sequencing and prenatal skeletal abnormalities: comprehensive review and meta-analysis and way forward"],"prefix":"10.3389","volume":"16","author":[{"given":"Mengting","family":"Jiang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cui","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhen","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/pd.5616","article-title":"Exome sequencing for perinatal phenotypes: the significance of deep phenotyping","volume":"40","author":"Aggarwal","year":"2019","journal-title":"Prenat. 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