System analysis of gene mutations and clinical phenotype in Chinese patients with autosomal-dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder mainly caused by mutation in PKD1/PKD2. However, ethnic differences in mutations, the association between mutation genotype/clinical phenotype, and the clinical applicable value of mutation detection are poorly understood. We made systematically analysis of Chinese ADPKD patients based on a next-generation sequencing platform. Among 148 ADPKD patients enrolled, 108 mutations were detected in 127 patients (85.8%). Compared with mutations in Caucasian published previously, the PKD2 mutation detection rate was lower, and patients carrying the PKD2 mutation invariably carried the PKD1 mutation. The definite pathogenic mutation detection rate was lower, whereas the multiple mutations detection rate was higher in Chinese patients. Then, we correlated PKD1/PKD2 mutation data and clinical data: patients with mutation exhibited a more severe phenotype; patients with >1 mutations exhibited a more severe phenotype; patients with pathogenic mutations exhibited a more severe phenotype. Thus, the PKD1/PKD2 mutation status differed by ethnicity, and the PKD1/PKD2 genotype may affect the clinical phenotype of ADPKD. Furthermore, it makes sense to detect PKD1/PKD2 mutation status for early diagnosis and prognosis, perhaps as early as the embryo/zygote stage, to facilitate early clinical intervention and family planning.