Identification of novel causative genes of monogenic diabetes

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08527
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Kyoto University
• Principal Investigator: Tanaka Daisuke 京都大学, 医学研究科, 助教 (50582904)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 糖尿病

Outline of Final Research Achievements

Type 1 and type 2 diabetes are thought to be polygenic disorders involving multiple genes. However,there are often cases of diabetes with characteristics such as early diagnosis, non-obesity, and familial accumulation, which suggest that diabetes is due to a mutation in a single gene, but only a few cases have been explained by known genes.
In this study, we performed a comprehensive analysis using whole-genome sequencing of genomic DNA for cases of diabetes diagnosed at a young age in which mutations could not be found in the 11 known genes that cause diabetes. As a result, we found a novel frameshift mutation in the RFX6 gene, which is involved in the development of the pancreas,in one case. We believe that we have been able to explore the genetic background of young-onset diabetes in more detail.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

若年診断糖尿病の発症に関与する遺伝的背景のひとつとしてRFX6遺伝子変異を同定したことで、若年診断糖尿病の成因の主たるものが膵β機能や膵発生に関与する遺伝子の異常であることをより明確にすることができた。本研究の成果を受けて、若年診断糖尿病においてRFX6をはじめとする膵発生に関与する遺伝子の解析が進めば、個々の遺伝子異常による糖尿病の臨床像が明確となり診療に役立つ。さらに、RFX6分子等をターゲットとした創薬により、当該遺伝子に変異を持つ糖尿病および一般の糖尿病の治療につながる可能性が示唆される。