{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:17:49Z","timestamp":1760141869279,"version":"build-2065373602"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"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>Waardenburg syndrome (WS) is a group of autosomal dominant hereditary disorders characterized by auditory\u2013pigmentary abnormalities. Haploinsufficiency of paired box 3 (<jats:italic>PAX3<\/jats:italic>) gene is one of the known pathogenic mechanisms. However, clinical phenotypes are difficult to predict precisely in fetuses harboring <jats:italic>PAX3<\/jats:italic> haploinsufficiency. In this study, we report a family with a <jats:italic>PAX3<\/jats:italic> deletion encompassing exons 1\u20134, in which clinical manifestations ranged from normal to mild abnormalities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>A 22-year-old woman (gravida 2, para 0) was referred to our prenatal center at 18\u2005weeks of gestation due to a history of congenital spina bifida in her previous pregnancy. Chromosomal analysis had been performed on fetal tissue from the terminated pregnancy and on amniotic fluid obtained during the current pregnancy. A rare partial deletion of <jats:italic>PAX3<\/jats:italic> gene was identified and confirmed to be of paternal origin. A diagnosis of WS was established based on the clinical features of the father. However, the newborn from the second pregnancy exhibited normal phenotypes after birth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This work suggests that deletions encompassing the promoter and functional domains of <jats:italic>PAX3<\/jats:italic> gene functionally represent a haploinsufficiency mechanism, which leads to variable clinical manifestations. These findings broaden our understanding of copy number variation analysis and genetic counseling in prenatal settings. In addition, <jats:italic>PAX3<\/jats:italic> gene should be considered a candidate gene in cases presenting with auditory\u2013pigmentary abnormalities or neural tube defects of unknown etiology.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1642132","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T04:20:14Z","timestamp":1760070014000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mild features of partial PAX3 deletion in patients with prenatal Waardenburg syndrome: a case report and literature 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