biostudies-literatureSewerin SDeutsche ForschungsgemeinschaftElse Kröner-Fresenius-Stiftungsfad260https://www.ebi.ac.uk/biostudies/studies/S-EPMC10783239biostudies-literatureUnknown17(1)<h4>Backgound</h4>Branchiootorenal (BOR) syndrome is an autosomal dominant disorder caused by pathogenic <i>EYA1</i> variants and clinically characterized by auricular malformations with hearing loss, branchial arch anomalies, and congenital anomalies of the kidney and urinary tract. BOR phenotypes are highly variable and heterogenous. While random monoallelic expression is assumed to explain this phenotypic heterogeneity, the potential role of modifier genes has not yet been explored.<h4>Methods</h4>Through thorough phenotyping and exome sequencing, we studied one family with disease presentation in at least four generations in both clinical and genetic terms. Functional investigation of the single associated <i>EYA1</i> variant c.1698+1G>A included splice site analysis and assessment of Clinical kidney journalMechanisms of pathogenicity and the quest for genetic modifiers of kidney disease in branchiootorenal syndrome.PMC10783239PE 3135/1–1HA 6908/3–1HA 6908/4–12019_A96SE 3451/1–1HA 6908/7–1HA 6908/8–1Rozman DDittrich KSewerin SBlagotinsek Cokan KPetzold FHalbritter JAurnhammer CMayer BSchonauer RSkubic CJeruc JPfister FfalseMechanisms of pathogenicity and the quest for genetic modifiers of kidney disease in branchiootorenal syndrome.<h4>Backgound</h4>Branchiootorenal (BOR) syndrome is an autosomal dominant disorder caused by pathogenic <i>EYA1</i> variants and clinically characterized by auricular malformations with hearing loss, branchial arch anomalies, and congenital anomalies of the kidney and urinary tract. BOR phenotypes are highly variable and heterogenous. While random monoallelic expression is assumed to explain this phenotypic heterogeneity, the potential role of modifier genes has not yet been explored.<h4>Methods</h4>Through thorough phenotyping and exome sequencing, we studied one family with disease presentation in at least four generations in both clinical and genetic terms. Functional investigation of the single associated <i>EYA1</i> variant c.1698+1G>A included splice site analysis and assessment of 2024-01-01T00:00:00Z2024 Jan2026-06-02T10:36:31.085Z2025-02-18T23:15:45.122ZS-EPMC107832393821348910.1093/ckj/sfad260