Mutation analyses by next-generation sequencing and multiplex ligation-dependent probe amplification in Japanese autosomal dominant polycystic kidney disease patients
Mutation analyses by next-generation sequencing and multiplex ligation-dependent probe amplification in Japanese autosomal dominant polycystic kidney disease patients
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DOI：
10.1007/s10157-019-01736-3
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发表时间：
2019-08-01
影响因子：
2.3
通讯作者：
Nitta, Kosaku
中科院分区：
文献类型：
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作者：
Mochizuki, Toshio;Teraoka, Atsuko;Nitta, Kosaku
背景常染色体显性遗传性多囊肾病（autosomaldominantpolycystickidney disease，ADPKD）是一种常见的遗传性肾脏疾病，其病因是肾脏囊肿逐渐增大，最终导致肾功能衰竭。由于下一代测序（NGS）的先进技术，致病基因PKD 1和PKD 2的遗传分析已经改进。方法我们进行了遗传分析的111例日本ADPKD患者使用杂交为基础的NGS和远程（LR）-PCR为基础的NGS。结果111例患者中，NGS的检出率为86.5%。MLPA检测到PKD 1基因第1外显子的1个突变和5个缺失。结论尽管NGS有一定的应用价值，但我们建议增加对PKD 1和MLPA外显子1的桑格测序，以发现NGS未检测到的突变。
Background Autosomal dominant polycystic kidney disease (ADPKD), one of the most common hereditary kidney diseases, causes gradual growth of cysts in the kidneys, leading to renal failure. Owing to the advanced technology of next-generation sequencing (NGS), genetic analyses of the causative genes PKD1 and PKD2 have been improved.Methods We performed genetic analyses of 111 Japanese ADPKD patients using hybridization-based NGS and long-range (LR)-PCR-based NGS. Additionally, genetic analyses in exon 1 of PKD1 using Sanger sequencing because of an extremely low coverage of NGS and those using multiplex ligation-dependent probe amplification (MLPA) were performed.Results The detection rate using NGS for 111 patients was 86.5%. One mutation in exon 1 of PKD1 and five deletions detected by MLPA were identified. When combined, the total detection rate was 91.9%.Conclusion Although NGS is useful, we propose the addition of Sanger sequencing for exon 1 of PKD1 and MLPA as indispensable for identifying mutations not detected by NGS.