Investigation of novel causative mutations for young-onset diabetes using next-generation sequencing

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08509
• 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): 2018-04-01 – 2021-03-31
• Keywords: 若年発症成人型糖尿病 / 次世代シーケンス

Outline of Final Research Achievements

The subjects of our study were patients diagnosed with antibody-negative diabetes before the age of 35 and their relatives. We selected 29 probands that were negative for known mutations in genes linked to maturity-onset diabetes of the young(MODY) and exome sequencing of their genome DNA was performed.
As a result, mutations in PTF1A gene(NC_000010.11:g.23192583C>T) and GATA6 gene (NC_000018.10:g.22171347A>T) were identified as candidates for novel causative mutations for young-onset diabetes.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

1型糖尿病や2型糖尿病は多因子遺伝疾患であるが、単一遺伝子異常により発症する糖尿病が知られており、これまでに30以上の原因遺伝子が明らかとなっている。
一方、若年発症で、単一遺伝子異常による糖尿病が疑われるが、いまだ原因遺伝子変異が同定されない症例は多い。新規原因遺伝子変異の同定により、各症例の病態解明のみならず、糖尿病発症の分子機序に迫ることができると考える。