Mutational Screening of PKD1 and PKD2 Genes in Iranian Population Diagnosed with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the fourth most frequent cause of endstage renal disease (ESDR), occurring at a varying frequency of 1/400 to 1/800 persons. The disease affects all ethnic groups worldwide, and there is a need for population based studies to be carried out for better diagnostic, genetic counselling, and treatment purpose.

METHODS: Eighteen unrelated probands (10 males and 8 females) with a familial history of ADPKD were selected for the study. Their clinical evaluation was performed to diagnose and assess disease progression. PKD1 and PKD2 genes were genotyped in each proband by next generation sequencing (NGS).

RESULTS: Mutational analysis of PKD1 and PKD2 genes using NGS in eighteen unrelated Iranian ADPKD families revealed a total of eighteen heterozygous variations. PKD1 genotype revealed eight frameshift deletion mutations, two frameshift insertion mutations, five nonsense mutations and one splice mutation and PKD2 showed one frameshift deletion mutation and one frameshift insertion mutation. Four of the variants reported were novel and were present in the PKD1 gene. Further, PKD1 truncating mutations reached ESRD earlier than patients with non-truncating PKD1 mutations (52 ± 3.2 years vs. 58 ± 10.8 years, p = 0.01).

CONCLUSIONS: The PKD1 and PKD2 genotyping of ADPKD Iranian patients with familial history showed no mutational hotspot. The screening has given four novel variants that will contribute to diagnosis, genetic counselling, and treatment of ADPKD patients in general.