Discovery of new causative genes for salt-losing nephropathy and elucidation of its pathological mechanism

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17733
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Mori Takayasu 東京医科歯科大学, 医学部附属病院, 助教 (00735813)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 遺伝子解析研究 / 塩喪失性腎症 / 次世代シークエンサー / パネル遺伝子診断

Outline of Final Research Achievements

A comprehensive genetic analysis of 84 adult patients with salt-losing nephropathy represented by Gitelman syndrome (GS) was performed, and investigation of about half of the unsolved cases revealed that they have several clinical characteristics. We reported that these cases may be categorized into new disease groups (Mori T, HumMutat. 2021). Including this, a total of 18 original papers were published during the period of this research, confirming the importance of genetic analysis for kidney diseases. In addition, experimental approaches were conducted on the two candidate genes (CACNA1H and SQSTM1) that had been the focus of attention from the beginning of the application, but unfortunately no significant findings have been obtained so far, and further verification is required. Whole exome sequences on the unsolved cases have been completed, and we will continue to verify multiple promising candidates.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

次世代シークエンシング技術（NGS）の登場により一度の解析で得られるゲノムデータ量は飛躍的に増加し、遺伝子検査は単なる個別疾患診断という枠組みを超え、大きな臨床的意義を持つようになった。今回Human Mutation誌に報告した塩喪失性疾患未解決群の臨床的特徴は、新しい疾患概念として再考される可能性があり、その病態解明は腎臓病学の発展に大きく寄与すると期待される。また塩喪失性腎症の新しい候補遺伝子探索は希少疾患の病態解明に止まらず、塩分摂取過多、飽食の時代における塩分感受性高血圧や臓器障害などのコモン病治療方策への展開としても、将来性を有すると期待される。