Genetic defects in ciliary genes in autosomal dominant polycystic kidney disease.

Aim: To evaluate the genetic defects of ciliary genes causing the loss of primary cilium in autosomal dominant polycystic kidney disease (ADPKD).

Methods: We analyzed 191 structural and functional genes of the primary cilium using next-generation sequencing analysis. We analyzed the kidney samples, which were obtained from 7 patients with ADPKD who underwent nephrectomy. Each sample contained polycystic kidney tissue and matched normal kidney tissue.

Results: In our study, we identified genetic defects in the 5 to 15 genes in each ADPKD sample. The most frequently identified defects were found in genes encoding centrosomal proteins (PCM1, ODF2, HTT and CEP89) and kinesin family member 19 (KIF19), which are important for ciliogenesis. In addition, pathogenic mutations in the PCM1 and KIF19 genes were found in all ADPKD samples. Interestingly, mutations in the genes encoding the intraflagellar transport proteins, which are the basis of animal models of ADPKD, were only rarely detected.

Conclusion: The results of our study revealed the actual state of structural ciliary genes in human ADPKD tissues and provided valuable indications for further research.