P615: Solving the unsolved: HiFi long-read sequencing reveals hidden structural variants in ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) affects approximately 1 in 1,000 individuals and accounts for 5–10% of end-stage kidney disease cases. The primary disease gene, PKD1, poses substantial technical challenges for genetic testing due to six highly homologous pseudogenes sharing 97–99% sequence identity, a transcript length exceeding 12-kb, high GC content and numerous polypyrimidine tracts. Traditionally, long-range PCR followed by Sanger sequencing has been regarded as the gold standard for PKD1 analysis; however, our recent study showed that clinical exome sequencing (ES) can provide a comparable and reliable diagnostic yield by exploiting unique bases that differentiate PKD1 from its pseudogenes.