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The etiology of BE is unknown but thought to be influenced by genetic variation with more recent studies suggesting a role for rare variants. As such, we conducted paired\u2010end exome sequencing in 26 child\/mother\/father trios. Three children had rare (allele frequency\u2009\u2264\u20090.0001 in several public databases) inherited variants in\n TSPAN4<\/jats:italic>\n , one with a loss\u2010of\u2010function variant and two with missense variants. Two children had loss\u2010of\u2010function variants in\n TUBE1<\/jats:italic>\n . Four children had rare missense or nonsense variants (one per child) in\n WNT3<\/jats:italic>\n ,\n CRKL<\/jats:italic>\n ,\n MYH9<\/jats:italic>\n , or\n LZTR1<\/jats:italic>\n , genes previously associated with BE. We detected 17 de novo missense variants in 13 children and three de novo loss\u2010of\u2010function variants\n (AKR1C2<\/jats:italic>\n ,\n PRRX1<\/jats:italic>\n ,\n PPM1D)<\/jats:italic>\n in three children (one per child). We also detected rare compound heterozygous loss\u2010of\u2010function variants in\n PLCH2<\/jats:italic>\n and\n CLEC4M<\/jats:italic>\n and rare inherited missense or loss\u2010of\u2010function variants in additional genes applying autosomal recessive (three genes) and X\u2010linked recessive inheritance models (13 genes). Variants in two genes identified may implicate disruption in cell migration (\n TUBE1<\/jats:italic>\n ) and adhesion (\n TSPAN4<\/jats:italic>\n ) processes, mechanisms proposed for BE, and provide additional evidence for rare variants in the development of this defect.\n <\/jats:p>","DOI":"10.1002\/ajmg.a.62439","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:48:21Z","timestamp":1628210901000},"page":"3028-3041","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Exome sequencing of child\u2013parent trios with bladder exstrophy: Findings in 26 children"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0249-8298","authenticated-orcid":false,"given":"Georgia","family":"Pitsava","sequence":"first","affiliation":[{"name":"Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human 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