ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is the common hereditary kidney disease, resulting from mutations in polycystic kidney disease 1 (PKD1) and polycystic kidney disease 2 (PKD2). Clinical data and genetic features of six Chinese families including ADPKD patients were analyzed via Next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification. In family A, the proband (II5) with polycystic kidney (PK), hypertension, left ventricular hypertrophy, and valvular heart disease exhibited a heterozygous nonsense mutation, c.5086C>T (p.Gln1696Ter), in PKD1 (NM_001009944). In family B, the proband (II3) with PK, polycystic liver (PL), hypertension, hypertrophy of the left ventricle and septum, valvular heart disease, chronic kidney disease (CKD) stage 5, bilateral renal calculi, and right inguinal hernia exhibited a heterozygous missense mutation, c.6695T>C (p.Phe2232Ser), in PKD1. In family C, the proband (III1) with PK, PL, seminal vesicle cyst, hypertension, CKD stage 3, hypertrophy of the left ventricle and septum, and valvular heart disease harbored a heterozygous nonsense mutation, c.662T>G (p.Leu221Ter), in PKD2 (NM_000297). In family D, the proband (III3) with PK, hypertension, and CKD stage 5 harbored a heterozygous missense mutation, c.8311G>A (p.Glu2771Lys), in PKD1. In family E, the proband (II1) with PK, PL, hypertension, and CKD stage 5 exhibited a heterozygous deletion mutation, exon15-22, in PKD1. In family F, the proband (II2) with PK, PL, CKD stage 3, hypertension, thickened interventricular septum, and valvular heart disease carried a heterozygous missense mutation, c.1649A>G (p.His550Arg), in PKD2. Thus, three novel mutation sites which are responsible for ADPKD were discovered in this study.
