{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T12:59:54Z","timestamp":1788699594024,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"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. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Genetic diseases exhibit significant clinical and genetic diversity, leading to a complex and challenging diagnostic process. Exploiting novel approaches is imperative for the molecular diagnosis of genetic diseases. In this study, we utilized whole-exome sequencing (WES) to facilitate early diagnosis in patients suspected of genetic disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective analysis included 144 patients diagnosed by singleton-WES Trio-WES between January 2021 and December 2023. We investigated the relevance of diagnosis rates with age, clinical presentation, and sample type.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 144 patients, 61 were diagnosed, yielding an overall diagnostic rate of 42.36%, with Trio-WES demonstrating a significantly higher diagnostic rate of 51.43% (36\/70) compared to singleton-WES at 33.78% (25\/74) (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.05). Global developmental delay had a diagnosis rate of 67.39%, significantly higher than muscular hypotonia at 30.43% (<jats:italic>p<\/jats:italic>\u2009&amp;lt;\u20090.01) among different clinical phenotypic groups. Autosomal dominant disorders accounted for 70.49% (43\/61) of positive cases, with autosomal abnormalities being fivefold more prevalent than sex chromosome abnormalities. Notably, sex chromosome abnormalities were more prevalent in males (80%, 8\/10). Furthermore, 80.56% (29\/36) of pathogenic variants were identified as <jats:italic>de novo<\/jats:italic> mutations through Trio-WES.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings highlight the effectiveness of WES in identifying genetic variants, and elucidating the molecular basis of genetic diseases, ultimately enabling early diagnosis in affected children.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1448895","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:39:14Z","timestamp":1728362354000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["The application of whole-exome sequencing in the early diagnosis of rare genetic diseases in children: a study from Southeastern 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