常染色体显性多囊肾病中纤毛基因的遗传缺陷
Genetic defects in ciliary genes in autosomal dominant polycystic kidney disease.
作者信息
Skalická Katarína, Hrčková Gabriela, Vaská Anita, Baranyaiová Ágnes, Kovács László
机构信息
Laboratory of Clinical and Molecular Genetics, Department of Paediatrics, Faculty of Medicine, Comenius University and University Children's Hospital, Bratislava 83340, Slovakia.
出版信息
World J Nephrol. 2018 Mar 6;7(2):65-70. doi: 10.5527/wjn.v7.i2.65.
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 (, , and ) and kinesin family member 19 (), which are important for ciliogenesis. In addition, pathogenic mutations in the and 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.
目的
评估导致常染色体显性多囊肾病（ADPKD）中初级纤毛缺失的纤毛基因的遗传缺陷。
方法
我们使用下一代测序分析来分析初级纤毛的191个结构和功能基因。我们分析了从7例接受肾切除术的ADPKD患者获取的肾脏样本。每个样本包含多囊肾组织和匹配的正常肾组织。
结果
在我们的研究中，我们在每个ADPKD样本中鉴定出5至15个基因的遗传缺陷。最常鉴定出的缺陷存在于编码中心体蛋白（、、和）以及驱动蛋白家族成员19（）的基因中，这些对纤毛发生很重要。此外，在所有ADPKD样本中均发现了和基因的致病突变。有趣的是，编码鞭毛内运输蛋白的基因中的突变很少被检测到，而这些基因是ADPKD动物模型的基础。
结论
我们的研究结果揭示了人类ADPKD组织中结构性纤毛基因的实际状况，并为进一步研究提供了有价值的线索。
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