Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the fourth most common cause of end-stage renal disease, occurring at a frequency of 1 in 400 to 1 in 800 individuals among different populations. The disease affects all ethnic groups worldwide, and there is a requirement for population-based studies to be conducted in order to improve diagnosis, genetic counseling and treatment. A large Iranian family with ADPKD was recruited for the current study. Clinical evaluation was performed to diagnose and assess disease progression in 11 members of this family, including 7 affected members and 4 unaffected members. PKD1 and PKD2 genes were genotyped in subjects by next-generation sequencing (NGS). Mutational analysis of PKD1 and PKD2 genes in this family revealed three intronic variations and three synonymous exonic variants in the PKD2 gene, and two non-synonymous exonic variants and eight intronic variants in PKD1, resulting in a total of 16 heterozygous variations among these two genes. Among the 16 variations, all except three intronic variants in the PKD1 gene have already reported in the Iranian population. The three novel mutations were predicted to be deleterious polymorphisms using in silico methods. Among the reported intronic variations, rs201204878 was identified as a splice region variant, leading to truncation of the polycystin-1 protein. In conclusion, genotyping of PKD1 and PKD2 in this family with ADPKD revealed no mutational hot spots. However, genetic screening identified three novel variants in the Iranian population. The data generated in the present study will contribute to improving the diagnosis, genetic counseling and treatment of patients with ADPKD.