Genetic defects in ciliary genes in autosomal dominant polycystic kidney disease

• 作者: Agnes Baranyaiová Anita Vaská Gabriela Hrcková Katarína Skalická László Kovács
• 来源期刊: 世界肾病学杂志：英文版
• 学科: 医学
• 关键词: POLYCYSTIC kidney disease Primary CILIUM CILIARY GENES Next-generation sequencing Genetic VARIANTS
• 年，卷（期）: 2018,（2）
• 页码范围: 65-70
• 页数: 6页
• 分类号: R

摘要

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.