Fig. 1

Genetic analysis pipeline. A total of 800 probands with iCKD will be enrolled in the study. They will be classified into typical ADPKD, atypical polycystic kidney disease, or other/pediatric iCKDs. For the first screening genetic test, a targeted gene panel of 89 cytogenesis-related genes will be applied to the total population. All the variants will be analyzed by bioinformaticians to identify pathogenic mutations. For those with variants of undetermined significance (VUS) or no variants found by the gene panel, different genetic approaches will be taken for each class of iCKD. For those with typical ADPKD, targeted exome sequencing of PKD1 after long-range PCR combined with MLPA will be performed to identify pathogenic mutations. If the mutations are not found by this method, WES will take place. For those with atypical polycystic kidney disease or pediatric iCKD, WES will be performed to identify pathogenic mutations. For the last step of genetic diagnosis, a family segregation study will be performed to elucidate the cause of genotype-phenotype discordance, in-family severity discordance, or discordance between renal and extrarenal manifestations. Abbreviations: ADPKD, autosomal dominant polycystic kidney disease; iCKD, inherited cystic kidney disease; PCR, polymerase chain reaction; MLPA, multiplex ligation-dependent probe amplification; PKD, polycystic kidney disease; VUS, variant of undetermined significance; WES, whole exome sequencing