Fig. 1: Study design and outcomes.

100 clinically diagnosed autosomal dominant polycystic kidney disease (ADPKD) families were genetically analyzed by next-generation sequencing (NGS)-based customized PKD gene panel and multiplex ligation-dependent probe amplification (MLPA). As a result, class 3–5 PKD1/2 variants were identified in 90 families (79 PKD1—red, although 9 of these were formally PKD1-VUS, 11 PKD2—blue). In the remaining 10 families without identification of class 3–5 PKD1/2 variants (PKD1/2-negative), panel diagnostics yielded two known heterozygous PKHD1 variants (yellow), indicating autosomal recessive PKD (ARPKD) in one family. In another two families, exome sequencing (ES) identified a pathogenic FLCN variant (yellow) and a pathogenic ALG9 variant (yellow) respectively. Among seven families who remained genetically unsolved (gray box), we identified four potential candidate gene variants in ALG6, GLI2, LRP5, and TSC2 (#) (Fig. S2). VUS variant of unknown significance.