Clinical Characteristics And Mutation Site Analysis Of Autosomal Dominant Polycystic Kidney Disease

Polycystic kidney disease(PKD)is the most common hereditary kidney disease.The major mutations that cause autosomal dominant polycystic kidney disease(ADPKD)are PKD1,PKD2 and some rare pathogenic genes.We included 78 patients with ADPKD in this study.Clinical characteristics were analyzed and multiple regression analysis was used to determine factors associated with estimated glomerular filtration rate(eGFR).The mean age of this group of patients was 56.7 years;the average age of first diagnosed ADPKD was 37.1 years,65(83.3%)patients had hypertension,and 64(82.1%)patients had polycystic liver disease.Hematuria was present in 20(25.6%)patients and urinary protein was positive in 43(55.1%)patients.The mean value of hemoglobin was 110.8 g/L,the average white blood cell count was 6.05×109/L,the average platelet count was 206.4×109/L,the average albumin was 38.4 g/L,and the mean serum creatinine was 328.8 umol/L.The average eGFR was 42.6 ml/min/1.73 m2.eGFR was negatively correlated with age and positively correlated with hemoglobin in patients with ADPKD.We performed gene sequencing on 44 patients with bilateral polycystic kidney disease and 3 patients with unilateral polycystic kidney disease.Forty-eight PKD1 and PKD2 mutation sites were detected in 42 bilateral PKD patients,of which Forty-two were PKD1 mutation sites(87.5%)and 6 were PKD2 mutation sites(12.5%).All of which exhibited typical ADPKD.Furthermore,we detected HNF1B heterozygous mutations in 3 families.Although these 3 patients showed HNF1B heterozygous mutations,their clinical characteristics differed and showed phenotypic heterogeneity.Our results show that targeted NGS panel was helpful in detecting typical ADPKD patients and even in non-typical PKD patients.Null variant(frameshift,multiexon deletion)in HNF1B may lead to bilateral polycystic kidney disease.The 16 novel PKD gene mutation sites and 2 novel PKD2 gene mutation sites discovered in this study have some significance in genetic counseling for ADPKD patients,and increase the number of studied families and expand the mutation database of ADPKD.