Mori Takayasu, Hosomichi Kazuyoshi, Chiga Motoko, Mandai Shintaro, Nakaoka Hirofumi, Sohara Eisei, Okado Tomokazu, Rai Tatemitsu, Sasaki Sei, Inoue Ituro, Uchida Shinichi
Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo, Tokyo, 113-8519, Japan.
Department of Bioinformatics and Genomics, Kanazawa University, Ishikawa, Japan.
Clin Exp Nephrol. 2017 Feb;21(1):63-75. doi: 10.1007/s10157-016-1252-1. Epub 2016 Feb 26.
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.
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.
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.
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.
通过DNA测序鉴定遗传性肾脏疾病的基因对于精确诊断、治疗和遗传咨询至关重要。然而，面对各种遗传性疾病中报告的致病基因数量不断增加，传统的桑格测序现在实际上已无能为力。新一代测序技术的出现使得能够对多个候选基因进行大规模、全基因组、同步序列分析。
我们设计并验证了一个针对约100种主要遗传性肾脏疾病的综合诊断面板，包括127个已知基因。该面板被命名为遗传性肾脏疾病简易、快速、高效诊断（SPEEDI-KID）。我们将该面板应用于来自56个家庭的73名临床诊断为遗传性肾脏疾病的个体。
该面板有效地覆盖了候选基因，并实现了快速准确的基因诊断。此外，还检测到18个疑似致病的未报告突变。所有这些突变均通过桑格测序验证，一致性达100%。
总之，我们开发了一种强大的诊断方法，即使用定制面板SPEEDI-KID专注于遗传性肾脏疾病，无论疾病类型如何，都能实现快速、简便和全面的诊断。
