Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel
Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel
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DOI：
10.1007/s10157-016-1252-1
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发表时间：
2017-02-01
影响因子：
2.3
通讯作者：
Uchida, Shinichi
中科院分区：
文献类型：
--
作者：
Mori, Takayasu;Hosomichi, Kazuyoshi;Uchida, Shinichi
背景：通过DNA测序对遗传性肾脏疾病的基因鉴定对于精确诊断、治疗和遗传咨询具有重要意义。然而，面对越来越多的各种遗传疾病的致病基因的报道，传统的Sanger测序现在实际上是无能为力的。新一代测序技术的出现使得对多个候选基因进行大规模、全基因组、同时测序分析成为可能。方法设计并验证了约100种主要遗传性肾脏疾病的综合诊断面板，其中包括127个已知基因。该小组被命名为遗传性肾脏疾病的简单、快速和有效诊断（SPEEDI-KID）。我们将该小组应用于来自56个家庭的73名临床诊断为遗传性肾脏疾病的个体。结果该图谱有效地覆盖了候选基因，实现了及时准确的遗传诊断。此外，还发现了18种未报告的突变，怀疑是疾病的原因。所有突变均经Sanger测序验证，一致性为100%。总之，我们开发了一种强大的诊断方法，专注于遗传性肾脏疾病，使用自定义面板SPEEDI-KID，无论疾病类型如何，都可以快速，简单，全面地诊断。
Background Gene identification of hereditary kidney diseases by DNA sequencing is important for precise diagnosis, treatment, and genetic consultations. However, the conventional Sanger sequencing is now practically powerless in the face of ever increasing numbers of reported causative genes of various hereditary diseases. The advent of next-generation sequencing technology has enabled large-scale, genome-wide, simultaneous sequence analyses of multiple candidate genes.Methods We designed and verified a comprehensive diagnosis panel for approximately 100 major inherited kidney diseases, including 127 known genes. The panel was named Simple, sPEedy and Efficient Diagnosis of Inherited KIdney Diseases (SPEEDI-KID). We applied the panel to 73 individuals, clinically diagnosed with an inherited kidney disease, from 56 families.Results The panel efficiently covered the candidate genes and allowed a prompt and accurate genetic diagnosis. Moreover, 18 unreported mutations suspected as the disease causes were detected. All these mutations were validated by Sanger sequencing, with 100 % concordance.Conclusion In conclusion, we developed a powerful diagnostic method, focusing on inherited kidney diseases, using a custom panel, SPEEDI-KID, allowing a fast, easy, and comprehensive diagnosis regardless of the disease type.