Establishment of the targeted NGS panel and the associated immune factors-test system for SRNS

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Kansai Medical University (2017-2018); Kobe University (2016)
• Principal Investigator: SHONO Akemi 関西医科大学, 医学部, 研究員 (10535066)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 遺伝性腎疾患 / ステロイド抵抗性ネフローゼ症候群 / 次世代シークエンサー / 疾患パネル解析

Outline of Final Research Achievements

This research design was approved by the Institutional Review Board of Kobe University School of Medicine, and the participants-derived samples and data from all affiliated institutes in Japan were collected by obtaining their written informed consents.
Genetic analysis using the targeted next generation sequencing panel (43-49 genes for SRNS/FSGS) was conducted on the affected individuals with congenital and infantile nephrotic syndrome, and steroid resistant nephrotic syndrome. The candidate mutations and their genetic segregation were confirmed by the Sanger sequencing. The causative genes were identified in an approximately 30% of the recruited familial or sporadic cases (67 out of 219 cases) to date. NPHS2 mutations were not identified in this study so far, resulting in reflection of the racial differences in the incidence compared to the Europe and the United states as reported.

Free Research Field

遺伝性腎疾患

Academic Significance and Societal Importance of the Research Achievements

欧州・米国・韓国においては、すでにいくつかSRNS/FSGS疾患パネルを用いた遺伝子解析と腎生検による病理学的組織所見や予後、長期フォローアップデータを統計学的にまとめた報告が出てきており、それを基にした治療方針の決定などが成されてきている。しかし、本邦では解析症例数の少なさと包括的データベースの構築が追いついておらず、患者背景や疾患発症機序に基づく検査診断体制の整備が立ち後れているのが現状である。本研究により、遺伝情報と免疫応答による複合的病態理解が進めば、副作用の少ない疾患特異的治療の開発につながり、患者QOLの向上が期待できる。