Search for novel disease causative genes and development of a phenotype-genotype database utilizing the comprehensive kidney disease diagnosis panel

2018 Fiscal Year Final Research Report

• Project/Area Number: 17H06657
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• 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): 2017-08-25 – 2019-03-31
• Keywords: 遺伝性腎疾患 / 塩喪失性腎症 / 次世代シークエンサー / パネル診断

Outline of Final Research Achievements

Comprehensive genetic testing using the next-generation sequencing (NGS) panel for diagnosis of inherited kidney diseases, which we introduced to nephrology field first, was applied to about 700 cases by 2018. At this moment, many definitive genetic diagnoses could be obtained. By accumulating undiagnosed cases and identifying common gene mutations among them, we aimed to discover novel disease causative genes and to find genotype-phenotype correlations from accumulated data. As a result, CACNA1H and SQSTM1 have been identified as new responsible gene candidates for salt-losing kidney diseases, and further investigation is currently ongoing. To discover novel responsible genes is not limited to only elucidation of the pathophysiology of rare diseases, but is also useful for development of treatment strategies for common diseases such as salt-sensitive hypertension and organ damages.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

我々は次世代高速シークエンサーという機器を用いた網羅的遺伝子検査を、世界にも先駆けて腎臓病領域に導入し、これまでに700例を超える症例に対して検査を行い、多くの遺伝子診断をしてきました。一方で原因が特定できない未診断例を集積し、それらの症例に共通する遺伝子変異を同定することで新たな疾患原因遺伝子の発見を目指しています。結果、塩喪失性腎臓病の新しい原因遺伝子候補としてCACNA1HやSQSTM1といった遺伝子が同定され、現在そのメカニズムを検証しています。最終的には希少疾患にとどまらずより一般的な疾患治療への応用を目指しています。