Retrospective investigation of PKD1 and PKD2 gene variants detected by next generation sequencing in patients with autosomal dominant polycystic kidney disease

Aim: Autosomal Dominant Polycystic Kidney Disease, is a multisystemic, clinically and genetically heterogeneous disease characterized by progressive renal cysts and renal failure. Its prevalence is 1/1000-1/2500. It mostly occurs due to mutations in PKD1 and PKD2 genes. Early diagnosis of the disease with genetic tests is very important in predicting the prognosis of patients and reproductive counseling. In this thesis, we aimed to retrospectively analyze the Next Generation Sequencing data in patients with ADPKD, to investigate and classify the detected variants, to bring new variants to the literature and to reveal the diagnostic value of PKD1 and PKD2 sequence analysis. Thus, it is planned to reveal the genetic diversity underlying the pathophysiology of the disease and to improve patient management. Material and Method: This study included 48 patients who underwent PKD1 and PKD2 sequence analysis in terms of ADPKD between 2017-2022 in İnönü University Faculty of Medicine Medical Genetics Polyclinic, and 48 aged matched controls who had the same NGS test for different clinic reasons. Demographic characteristics, family history and NGS data of patients and controls were reviewed retrospectively. Diagnosis rate was calculated with pathogenic, likely pathogenic and variant of unknown significance variants. Results: A total of 85 variants were detected in PKD1 and 12 variants in PKD2. 63 of them were classified as benign, likely benign. Of the 34 mutations, 11 were P, 11 were MP, and 12 were VUS, and the most common mutations were PKD1-missense (38.8%), PKD1-nonsense (26.4%) and PKD1-frameshift (17.6%). 67 variants were detected in the control group. In total, 12 novel variants detected in PKD1. P+MP variant was detected in 27 patients (56.25%) and VUS variant was detected in 8 patients. Of the 35 patients (72.9%) with a causative mutation, 26 (74.2%) had PKD1, 9 (25.7%) had PKD2 mutations. Conclusion: This study demonstrate the genetic diversity underlying ADPKD in the Turkish population. Keywords: Autosomal dominant polycystic kidney disease, ADPKD, PKD1, PKD2, next generation sequencing