identification of novel pathogenic pkd2 variants in iranian patients with autosomal dominant polycystic kidney disease

Background: autosomal dominant polycystic kidney disease (adpkd) is a delayed-onset renal disorder that results from a mutation in the pkd1 or pkd2 genes. autosomal dominant polycystic kidney disease results in end-stage renal disease due to renal cystic dysplasia. the aim of this study was to evaluate, by exon sequencing, the disease-causing variants of pkd2 (exons 4, 6, and 8) in iranian adpkd patients.methods: genomic dna was extracted from 3-5 ml of peripheral blood by the salting-out method. pkd2 exons 4, 6, and 8 were pcr-amplified and sequenced.results: three disease-causing pkd2 variants were identified; all three were missense mutations in exon 4. the mutations were agc → acc (c.893g>c, cdna.959g>c, s298t), tac → ttc (c.1043a>t, cdna.1109 a>t, y348f), and gaa → gat (c.1059a>t, cdna.1125 a>t, e353d. these novel pathogenic variants may cause loss of the normal protein function.conclusions: our results suggest that agc → acc (c.893g>c, cdna.959g>c, s298t), tac → ttc (c.1043a>t, cdna.1109 a>t, y348f), and gaa → gat (c.1059a>t, cdna.1125 a>t, e353d variants are common in iranian adpkd patients. these mutations modify the transmembrane domain and likely influence pc2 function.