Investigation of polycystic kidney disease by molecular methods

Aim: Polycystic kidney disease (PKD), which affects millions of people worldwide and is known as the most common cause of end-stage renal disease (ESRD), is a clinically and genetically heterogeneous group. PKD, one of the most common life-threatening genetic disorders caused by single gene mutations, inherited as autosomal dominant (ADPKD) and autosomal recessive (ARPKD). ADPKD is mostly caused by mutations in the Polycystic Kidney Disease 1 (PKD1) and Polycystic Kidney Disease 2 (PKD2) genes, while ARPKD is mostly caused by mutations in the Polycystic Kidney and Hepatic Disease 1 (PKHD1) gene. With genetic research in PKD, a definitive diagnosis of the disease can be made, the prognosis of the disease can be predicted, patients suitable for treatment can be selected and the treatment method can be determined, genetic counseling can be given for family planning and can be guidance in kidney transplant options. More reliable results can be obtained in a shorter time by the gene-targeted analysis methods of Next Generation Sequencing (NGS) technology, in which more than hundred genes are elucidated in hereditary kidney diseases. In our study, it was aimed to investigate mutations in the PKD1, PKD2 and PKHD1 genes in patients with PKD using the NGS method, to compare the phenotype-genotype relationship, to contribute to the literature of the new mutations that can be obtained, and to help early diagnosis and treatment by using them as disease-specific biomarkers. Materials and Methods: The pedigrees of thirty one patients included in the study group were drawn, their inheritance types were determined, and their clinical data and blood samples were collected. After DNA isolation and purity evaluation of the samples were completed, library preparation and target enrichment processes were completed, were loaded into the NGS device and the study was started. Bioinformatics analysis of the results was performed using databases. The phenotype-genotype relationship of the obtained results was evaluated. Results: As a result of the analysis of NGS data, a total of eighty five variants detected in the PKD1 gene; 3.53 % is pathogenic (P), 5.88 % is likely pathogenic (LP), 24.71 % is of unknown clinical significance (VUS), 51.76 % is benign (B), % 14.12 of them were evaluated as likely benign (LB). 62.50 % of the "P" and "LP" variants detected in the PKD1 gene and 23.81 % of the "VUS" variants were evaluated as "Novel" variants. A total of ten variants detected in the PKD2 gene; 20 % were evaluated as "P", 10 % as "VUS", 50 % as "B", and 20 % as "LB". Of the fifty six variants detected in the PKDH1 gene, 1.79 % were evaluated as "LP", 30.36 % as "VUS", and 67.86 % as "B". The only "LP" variant detected in the PKHD1 gene was "Novel" and 29.41% of "VUS" variants were evaluated as "Novel" variants. When the variants detected in the genes were evaluated together with the clinical data of the patients, phenotype-genotype relationships were found to be compatible. Conclusion: The data obtained in our study was aimed to contribute to future research focusing on diagnosis, prognosis and potential therapeutic interventions in PKD. Our results may contribute to a more in-depth understanding of the genetic factors underlying PKD and to early diagnosis and treatment by using it as a disease-specific biomarker. Our original results obtained for the first time from Manisa province in the Aegean region and the variants evaluated as "Novel" will be included in the databases and can be a reference for researchers who will work on this subject.